CGT Plus

Ichthyosis, congenital, autosomal recessive, type 4A; ICAR, type 4B (harlequin)

Descripción enfermedad:
Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of disorders of keratinization characterized primarily by abnormal skin scaling over the whole body. These disorders are limited to skin, with approximately two-thirds of patients presenting severe symptoms. The main skin phenotypes are lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur (Fischer, 2009). Neither histopathologic findings nor ultrastructural features clearly distinguish between NCIE and LI. In addition, mutations in several genes have been shown to cause both lamellar and nonbullous ichthyosiform erythrodermal phenotypes (Akiyama et al., 2003). At the First Ichthyosis Consensus Conference in Soreze in 2009, the term 'autosomal recessive congenital ichthyosis' (ARCI) was designated to encompass LI, NCIE, and harlequin ichthyosis (ARCI 4B; 242500) (Oji et al., 2010).NCIE is characterized by prominent erythroderma and fine white, superficial, semiadherent scales. Most patients present with collodion membrane at birth and have palmoplantar keratoderma, often with painful fissures, digital contractures, and loss of pulp volume. In half of the cases, a nail dystrophy including ridging, subungual hyperkeratosis, or hypoplasia has been described. Ectropion, eclabium, scalp involvement, and loss of eyebrows and lashes seem to be more frequent in NCIE than in lamellar ichthyosis (Fischer et al., 2000). In LI, the scales are large, adherent, dark, and pigmented with no skin erythema. Overlapping phenotypes may depend on the age of the patient and the region of the body. The terminal differentiation of the epidermis is perturbed in both forms, leading to a reduced barrier function and defects of lipid composition in the stratum corneum (Lefevre et al., 2006).In later life, the skin in ARCI may have scales that cover the entire body surface, including the flexural folds, and the scales are highly variable in size and color. Erythema may be very mild and almost invisible. Some affected persons exhibit scarring alopecia, and many have secondary anhidrosis (Eckl et al., 2005).

c.7444C>T;c.7323delC;c.6610C>T;c.6353C>G;c.6234-1G>C;c.5787T>G;c.5414C>G;c.5381+1G>C;c.5231G>A;c.5128+2T>C;c.5012delA;c.4615G>A;c.4541G>A;c.4142G>A;c.4139A>G;c.4108G>T;c.3889C>T;c.3256A>T;c.2593-1G>A;c.2296C>T;c.2273dupT;c.2140C>T;c.2121+2T>G;c.1660C>T;c.1657+1G>T;c.1300C>T;c.859C>T;c.596G>A;c.178C>T

Cholestasis, benign recurrent intrahepatic, type 2; Cholestasis, progressive familial intrahepatic, type 2

Descripción enfermedad:
Benign recurrent intrahepatic cholestasis is characterized by intermittent episodes of cholestasis without progression to liver failure. The cholestatic attacks vary in severity and duration and patients are asymptomatic between episodes, both clinically and biochemically (van Mil et al., 2004). Mutation in the ABCB11 gene can also cause cholestasis, progressive familial intrahepatic, type 2, a severe form of liver disease, which typically leads to liver failure. In people with PFIC, liver cells are less able to secrete a digestive fluid called bile. The buildup of bile in liver cells causes liver disease in affected individuals.

c.3767dupC;c.3692G>A;c.3457C>T;c.3268C>T;c.3213+1delG;c.3169C>T;c.3148C>T;c.2944G>A;c.2783_2787dupGAGAT;c.2782C>T;c.2380C>T;c.2296G>A;c.2178+1G>A;c.1966_1967delTT;c.1810-1G>A;c.1723C>T;c.1460G>A;c.1445A>G;c.1408C>T;c.1295G>C;c.1271delA;c.1069G>T;c.908+1delG;c.908+1G>A;c.890A>G;c.847G>T;c.409G>T;c.390-1G>T;c.379delA;c.167C>G;c.150+1G>A;c.22C>T

Hyperinsulinemic hypoglycemia, type 1 (congenital hyperinsulinism); Permanent neonatal diabetes mellitus (PNDM)

Descripción enfermedad:
Hyperinsulinemic hypoglycemia, also referred to as congenital hyperinsulinism or familial hyperinsulinism, is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur (Thornton et al., 1998). Furthermore, some mutations in the ABCC8 gene have been found to cause permanent neonatal diabetes mellitus (PNDM). PNDM is a type of diabetes that first appears within the first 6 months of life and persists throughout the lifespan. This form of diabetes is characterized by high blood sugar levels (hyperglycemia) resulting from a shortage of the hormone insulin. Individuals with PNDM experience slow growth before birth (intrauterine growth retardation). Affected infants have hyperglycemia and an excessive loss of fluids (dehydration) and are unable to gain weight and grow at the expected rate (failure to thrive). In some cases, people with PNDM also have certain neurological problems, including developmental delay and recurrent seizures (epilepsy). This combination of developmental delay, epilepsy, and neonatal diabetes is called DEND syndrome. Intermediate DEND syndrome is a similar combination but with milder developmental delay and without epilepsy. A small number of individuals with PNDM have an underdeveloped pancreas. Because the pancreas produces digestive enzymes as well as secreting insulin and other hormones, affected individuals experience digestive problems such as fatty stools and an inability to absorb fat-soluble vitamins. Most clinical cases for the previous two phenotypes have autosomal recessive inheritance but dominant cases have been detected too. Remarkably, certain mutations in this gene can cause the dominant phenotypes noninsulin-dependent diabetes mellitus and hypoglycemia of infancy, leucine-sensitive.

c.4631T>C;c.4618G>A;c.4567G>A;c.4556T>G;c.4548+2T>G;c.4519G>A;c.4481G>A;c.4480C>T;c.4477delG;c.4459_4460delAG;c.4454G>A;c.4454G>T;c.4453G>A;c.4435G>A;c.4415-2A>G;c.4414G>A;c.4379T>G;c.4371C>G;c.4356G>A;c.4325delC;c.4311-2A>G;c.4310G>A;c.4309C>T;c.4273A>G;c.4268C>G;c.4261C>T;c.4201G>A;c.4181G>A;c.4177T>G;c.4163_4165delTCT;c.4160_4162delCCT;c.4160C>T;c.4154_4155delAG;c.4149T>G;c.4139G>A;c.4139G>T;c.4138C>A;c.4138C>T;c.4123-1G>T;c.4122+1delG;c.4122+1G>A;c.4112C>T;c.4075_4076delAAinsT;c.4058G>A;c.4058G>C;c.4029_4030insC;c.4024C>T;c.3992-9G>A;c.3871-1G>A;c.3757-1G>A;c.3757-2A>G;c.3756+1G>A;c.3751C>T;c.3653+2T>A;c.3643C>T;c.3596C>T;c.3577delG;c.3560+1G>A;c.3560+1G>T;c.3557C>A;c.3548G>A;c.3547C>T;c.3545T>G;c.3528C>G;c.3520G>A;c.3512delT;c.3451_3452delGT;c.3403-1G>A;c.3402+1G>A;c.3127_3129delACCinsCAGCCAGGAACTG;c.3111G>A;c.3110G>A;c.2995C>T;c.2924-9G>A;c.2860C>T;c.2838_2841delGAGA;c.2800C>T;c.2698-1G>C;c.2698-2A>T;c.2697+1G>C;c.2686dupC;c.2559+1G>A;c.2509C>T;c.2298_2310delGAGAGGCCCCGTGinsAA;c.2295-1G>A;c.2258+2T>C;c.2222+1G>A;c.2222+1G>T;c.2202delA;c.2147G>T;c.2124_2127delGACT;c.2117-1G>A;c.2116+2T>C;c.2116+1G>A;c.2116+1G>T;c.2098_2099delAC;c.2041-1G>A;c.1879delC;c.1817+1G>T;c.1792C>T;c.1752delT;c.1732_1746dupGCCTCCCTCTCCCTC;c.1744C>G;c.1671+1G>C;c.1634delT;c.1630+1G>T;c.1616A>G;c.1606T>C;c.1603_1604insA;c.1562G>A;c.1536C>G;c.1532T>C;c.1468-2A>C;c.1467+2T>C;c.1467+1G>T;c.1347_1348delGA;c.1177-1G>A;c.1144G>A;c.1012-2A>G;c.823-1G>A;c.795dupG;c.742C>T;c.692G>A;c.683G>A;c.674T>C;c.638T>G;c.631C>A;c.627C>A;c.584dupA;c.579+2T>A;c.563A>G;c.560T>A;c.536_539delATGG;c.512dupT;c.415delC;c.413-2A>G;c.404T>C;c.394T>C;c.394T>G;c.331G>A;c.291-2A>G;c.290+2T>C;c.257T>C;c.257T>G;c.239T>G;c.221G>A;c.215A>G;c.149-1G>A;c.148+2T>G;c.134C>T;c.72C>A;c.62T>A

Adrenoleukodystrophy

Descripción enfermedad:
Adrenoleukodystrophy is an X-linked disorder which is secondary to a mutation in the ABCD1 gene and results in the apparent defect in peroxisomal beta oxidation and the accumulation of the saturated very long chain fatty acids (VLCFA) in all tissues of the body. The manifestations of the disorder occur primarily in the adrenal cortex, the myelin of the central nervous system, and the Leydig cells of the testes.ABCD1 is an ATPase binding cassette protein in the same category of transporter proteins such as the CFTR and MDR proteins.Identification of X-ALD as a lipid-storage disease, as a defect in the capacity to degrade VLCFAs, and its characterization as a peroxisomal disorder was reviewed by Moser (1997). Moser et al. (2005) provided a clinical review of ALD.

c.253dupC;c.311G>A;c.320T>C;c.346G>A;c.421G>A;c.442A>T;c.443A>G;c.454C>T;c.488G>A;c.520T>G;c.521A>G;c.529C>T;c.537_544dupCTACTACC;c.565C>T;c.614C>A;c.651G>C;c.761C>T;c.796G>A;c.838C>T;c.874_876delGAG;c.871G>A;c.886T>C;c.887A>G;c.1076_1077delAG;c.1082-1G>A;c.1096A>T;c.1126G>T;c.1166G>A;c.1252C>T;c.1270C>T;c.1288C>T;c.1366dupC;c.1390C>T;c.1396C>T;c.1415_1416delAG;c.1429G>T;c.1451C>G;c.1532G>A;c.1534G>A;c.1544C>T;c.1552delC;c.1552C>G;c.1552C>T;c.1553G>A;c.1586G>A;c.1628C>T;c.1634+1G>A;c.1635-2A>G;c.1660C>A;c.1661G>A;c.1679C>T;c.1771C>T;c.1772G>A;c.1780+2T>G;c.1781-1G>A;c.1802G>A;c.1817C>T;c.1825G>A;c.1826A>G;c.1849C>T;c.1850G>A;c.1865+1G>A;c.1866-10G>A;c.1866-1G>A;c.1866-1G>C;c.1876G>A;c.1895C>T;c.1978C>T;c.1992-2A>G;c.2006_2007delAC;c.2037G>A

Acyl-CoA dehydrogenase 9 deficiency (mitochondrial complex I deficiency, nuclear, type 20)

Descripción enfermedad:
Acyl-CoA dehydrogenase 9 deficiency, also known as mitochondrial complex I deficiency, nuclear, type 20, follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ACAD9 gene located on chromosomal region 3q21.3. The age of onset is neonatal/infantile. This disease is a multisystem disorder characterized by infantile onset of acute metabolic acidosis, hypertrophic cardiomyopathy, and muscle weakness associated with a deficiency of mitochondrial complex I activity in muscle, liver, and fibroblasts (summary by Haack et al., 2010).

c.23delT;c.130T>A;c.359delT;c.453+1G>A;c.509C>T;c.514G>A;c.797G>A;c.976G>C;c.1030-1G>A;c.1240C>T;c.1249C>T;c.1594C>T;c.1687C>G;c.1693-2A>G;c.1715G>A

Medium-chain acyl-CoA dehydrogenase deficiency

Descripción enfermedad:
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ACADM gene located on chromosomal region 1p31. Inherited deficiency of MCAD is a condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting). Signs and symptoms of MCAD deficiency typically appear during infancy or early childhood and can include vomiting, lack of energy (lethargy), and low blood sugar (hypoglycemia). Individuals with MCAD deficiency are at risk of serious complications such as seizures, breathing difficulties, liver problems, brain damage, coma, and sudden death. The estimated prevalence is 1:4,900-1:27,000 in Caucasian populations and 1:14,600 in worldwide populations.

c.30+2T>C;c.107_113dupGATTTAG;c.118+1G>T;c.157C>T;c.173_174delAG;c.216+1G>T;c.216+2T>G;c.224delT;c.233T>C;c.244dupT;c.250C>T;c.253G>A;c.270_271delCA;c.286+2T>G;c.386-2A>G;c.386-1G>C;c.421_424delATTA;c.419T>C;c.446G>A;c.461C>T;c.486+1delG;c.486+1G>A;c.486+1G>T;c.525delG;c.530_533delAGTA;c.536delT;c.548_551delCTGA;c.546G>A;c.563T>C;c.568-2A>C;c.568-1G>A;c.676A>G;c.682G>A;c.698+1G>A;c.698+2T>C;c.699-18G>A;c.715C>T;c.716G>A;c.716G>T;c.797T>C;c.807+1G>A;c.807+2T>G;c.808-2A>C;c.808-1G>A;c.829T>C;c.833C>T;c.841A>G;c.896A>G;c.898G>A;c.916_928delGCAATGGGAGCTT;c.948+1G>A;c.949-2A>G;c.981_982delAG;c.980G>C;c.1012G>T;c.1025dupT;c.1045-2A>C;c.1048C>T;c.1056_1057delAT;c.1058C>A;c.1076T>C;c.1083delG;c.1084A>G;c.1098_1110dupTAGAATGAGTTAC;c.1111_1112insTAGAATGAGTTAC;c.1111C>T;c.1144delC;c.1144C>T;c.1151C>T;c.1172delA;c.1201_1204delTTAG;c.1213dupG;c.1223T>C;c.1249G>T;c.1288dupT;c.1293+1G>A;c.1294-2A>T;c.1294-1G>C

Short-chain acyl-CoA dehydrogenase deficiency

Descripción enfermedad:
Short-chain acyl-CoA dehydrogenase deficiency follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ACADS gene located on chromosomal region 12q24.31. The age of onset is infantile. This disease is characterized by seizures, developmental delay, failure to grow with poor feeding, and usually muscle weakness and hypotonia. The prevalence is <1:50,000.

c.125_135delTCCAGACATGC;c.136C>T;c.164C>T;c.211-1G>A;c.238delC;c.274G>T;c.310_312delGAG;c.315delC;c.319C>T;c.369C>G;c.409C>T;c.417G>A;c.417G>C;c.473-2A>G;c.527C>A;c.529T>C;c.561_568delCAATGCCT;c.593_594delTT;c.675dupG;c.682_683delGA;c.910dupC;c.974G>A;c.988C>T;c.1029+1G>A;c.1030-1G>A;c.1031delA;c.1084C>T;c.1086+1G>A;c.1086+1G>T;c.1095G>T;c.1138C>T;c.1147C>T;c.1164_1165delTG

Very long-chain acyl-CoA dehydrogenase deficiency

Descripción enfermedad:
Very long-chain acyl-CoA dehydrogenase deficiency follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ACADVL gene located on chromosomal region 17p13.1. The age of onset is neonatal/infantile. This disease is characterized by cardiomyopathy, hypoketotic hypoglycemia, liver disease, exercise intolerance and rhabdomyolysis. The prevalence is 1:100,000-9:100,000.

c.132-2A>C;c.134C>A;c.174_178dupTGCCC;c.173delC;c.207+1G>A;c.207+2T>C;c.261delA;c.279dupT;c.320_321delCA;c.325C>T;c.335delC;c.346+1G>T;c.346+2T>G;c.347-1G>A;c.367_368delCA;c.368_374delAGTTTCT;c.377_378delAA;c.385_394delGTGGAGCCTG;c.411+1G>C;c.412delG;c.457_459delGAG;c.467G>A;c.469C>T;c.502C>T;c.546+1G>C;c.547-1G>C;c.566_567delTC;c.589G>A;c.602T>C;c.622G>A;c.671_672delAC;c.672C>G;c.706G>A;c.713_716delGTCT;c.733G>A;c.754C>T;c.777_778delCT;c.822-2A>C;c.848C>T;c.868_871delGTTA;c.898_900delGAG;c.917T>C;c.938dupG;c.934G>A;c.950_953dupGGCC;c.956_957delCT;c.965_967delAGA;c.960delG;c.1001delT;c.1022C>T;c.1025C>A;c.1065delT;c.1065dupT;c.1146_1146+1delGGinsCAC;c.1146+1G>A;c.1146+1G>T;c.1146+2T>C;c.1165C>T;c.1166G>A;c.1172A>C;c.1175T>C;c.1182delG;c.1210_1212delGAG;c.1213A>C;c.1215G>C;c.1251+1G>A;c.1251+2T>C;c.1252-15A>G;c.1252-1G>A;c.1315G>A;c.1338+1G>A;c.1349G>A;c.1352delA;c.1385dupG;c.1391G>A;c.1402-2A>T;c.1418G>A;c.1424dupT;c.1426C>T;c.1427G>A;c.1436G>A;c.1441T>C;c.1444dupC;c.1445G>A;c.1458dupG;c.1457G>A;c.1474C>T;c.1475G>A;c.1503+2T>G;c.1537G>C;c.1573C>G;c.1601G>A;c.1601+1G>A;c.1601+2T>C;c.1662dupG;c.1675-2A>C;c.1675-1G>A;c.1748-6G>A;c.1799_1809delCCATGGTGGTG;c.1817C>G;c.1834delC;c.1839_1842delTGAG;c.1875_1876delCT;c.1906C>T;c.1912C>T;c.1913G>A;c.1951delC

Alpha-methylacetoacetic aciduria (3-ketothiolase deficiency)

Descripción enfermedad:
Alpha-methylacetoacetic aciduria, also known as 3-ketothiolase deficiency, is an inborn error of isoleucine catabolism characterized by urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, tiglylglycine, and 2-butanone. This deficiency follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ACAT1 gene located on chromosomal region 11q22.3. The age of onset is neonatal/infantile. This disease is characterized by normal early development followed by a progressive loss of mental and motor skills. The prevalence is < 1:1,000,000.

c.2T>A;c.149delC;c.278A>G;c.412_419delCAAAGTCT;c.433C>G;c.444_445delGG;c.455G>C;c.472A>G;c.473A>G;c.547G>A;c.622C>T;c.653C>T;c.730+2T>C;c.757G>A;c.814C>T;c.826+1G>T;c.890C>T;c.905delA;c.935T>C;c.997G>C;c.1006-2A>C;c.1006-1G>C;c.1035_1037delAGA;c.1083dupA;c.1136G>T;c.1138G>A;c.1160T>C;c.1163+2T>C

Peroxisomal acyl-CoA oxidase deficiency

Descripción enfermedad:
Peroxisomal acyl-CoA oxidase deficiency follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ACOX1 gene located on chromosomal region 17q25.1. The age of onset is neonatal/infantile. This disease is characterized by hypotonia and seizures in the neonatal period and neurological regression in early infancy. The prevalence is < 1:1,000,000.

c.1851delT;c.926A>G;c.832A>G;c.591delG;c.532G>T;c.442C>T

Severe combined immunodeficiency due to adenosine deaminase deficiency (ADA)

Descripción enfermedad:
Severe combined immunodeficiency due to adenosine deaminase deficiency follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ADA gene located on chromosomal region 20q13.12. The age of onset is neonatal/infantile. This disease is characterized by profound lymphopenia and very low immunoglobulin levels of all isotypes resulting in severe and recurrent opportunistic infections. The annual incidence is 1:200,000-1:1,000,000. The prevalence is 1:100,000-9:100,000.

c.1078+2T>A;c.986C>T;c.956_960delAAGAG;c.911T>G;c.890C>A;c.872C>G;c.872C>T;c.845+1G>C;c.736C>T;c.704G>A;c.703C>T;c.698C>T;c.646G>A;c.632G>A;c.603C>G;c.532delG;c.532dupG;c.478+1G>A;c.467G>A;c.466C>T;c.424C>T;c.396dupA;c.350G>A;c.320T>C;c.302G>A;c.221G>T;c.219-1G>A;c.219-2A>G;c.218+2T>G;c.218+1G>A;c.95+1G>A;c.58G>A;c.43C>G;c.33+1G>C;c.7C>T

Ehlers-Danlos syndrome, dermatosparaxis type

Descripción enfermedad:
Ehlers-Danlos syndrome, dermatosparaxis type follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ADAMTS2 gene located on chromosomal region 5q35.3. The age of onset is neonatal/infantile. This disease is characterized by extremely fragile tissues, hyperextensible skin and easy bruising. The prevalence is <1:1,000,000.

c.3070delA;c.2458-6_2458delGCACAGG;c.2384G>A;c.673C>T

Aspartylglucosaminuria (glycosylasparaginase deficiency)

Descripción enfermedad:
Aspartylglucosaminuria, also known as glycosylasparaginase deficiency, follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the AGA gene located on chromosomal region 4q34.3. The age of onset is infantile. This disease is characterized by slowly developping mental retardation, beginning with clumsiness, late speech, and hyperkinesia, mild facial dysmorphism, and slight kyphoscoliosis.

c.941-2A>G;c.940+1G>A;c.940+1G>T;c.916T>C;c.904G>A;c.800delT;c.800dupT;c.788delT;c.770C>T;c.755G>A;c.754G>C;c.698+1G>T;c.676+1G>A;c.623-2A>G;c.537C>A;c.508-2A>G;c.503G>A;c.490C>T;c.488G>C;c.473G>A;c.439T>C;c.404T>C;c.373_376delACAC;c.369_373delACACA;c.346C>T;c.336delT;c.333delT;c.319C>T;c.302C>T;c.299G>A;c.281+1G>T;c.214T>C;c.200_201delAG;c.192delT;c.192T>A;c.127+1G>A;c.102_108delGCCCTTT;c.101_107delGGCCCTT

Glycogen storage disease, type 3

Descripción enfermedad:
Glycogen storage disease (GSD), type 3 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the AGL gene located on chromosomal region 1p21.2. The age of onset is infantile. This metabolic disorder is caused by deficiency of the glycogen debrancher enzyme and is associated with an accumulation of abnormal glycogen with short outer chains. Most patients are enzyme-deficient in both liver and muscle (IIIa), but about 15% are enzyme-deficient in liver only (IIIb) (Shen et al., 1996). These subtypes have been explained by differences in tissue expression of the deficient enzyme (Endo et al., 2006). In rare cases, selective loss of only 1 of the 2 debranching activities, glucosidase or transferase, results in type IIIc or IIId, respectively (Van Hoof and Hers, 1967; Ding et al., 1990). Clinically, patients with GSD type 3 present in infancy or early childhood with hepatomegaly, hypoglycemia, and growth retardation. Muscle weakness in those with IIIa is minimal in childhood but can become more severe in adults; some patients develop cardiomyopathy (Shen et al., 1996).

c.16C>T;c.18_19delGA;c.22delC;c.22C>T;c.64delC;c.82+1G>A;c.94C>T;c.100C>T;c.104T>G;c.118C>T;c.121G>T;c.140dupA;c.223_224delGA;c.251dupA;c.256C>T;c.276delG;c.289C>T;c.293+1delG;c.294-2A>T;c.294-1G>C;c.378T>A;c.437delG;c.442delA;c.460+1G>A;c.500dupG;c.535_538delTTAG;c.664+1G>A;c.664+3A>G;c.672dupT;c.753_756delCAGA;c.853C>T;c.958+1G>A;c.1078C>T;c.1082+1G>C;c.1159C>T;c.1169_1172delACTA;c.1185+1G>A;c.1222C>T;c.1384delG;c.1391dupG;c.1400delC;c.1423+1G>T;c.1485delT;c.1533dupA;c.1536_1545delCACTGAAATA;c.1589C>G;c.1597_1598delCT;c.1612-1G>C;c.1735+1G>T;c.1782C>A;c.1783C>T;c.1999delC;c.2001+2T>C;c.2011_2012delGT;c.2039G>A;c.2120_2121delAA;c.2158-2A>G;c.2158-1G>A;c.2223_2224delGT;c.2278delA;c.2309-1G>A;c.2457_2460delACAA;c.2525delC;c.2538dupT;c.2590C>T;c.2605C>T;c.2681+1G>A;c.2681+1G>T;c.2682-2A>G;c.2717_2721delAGATC;c.2728C>T;c.2906_2907delAT;c.2929C>T;c.2949+2T>A;c.2949+2T>C;c.2950-2A>C;c.2950-1G>A;c.3011delC;c.3083+2T>C;c.3204_3205delTA;c.3216_3217delGA;c.3235C>T;c.3297G>A;c.3362+1G>A;c.3363-1G>A;c.3439A>G;c.3443dupA;c.3444C>G;c.3554delC;c.3589-1G>A;c.3613C>T;c.3652C>T;c.3682C>T;c.3807dupT;c.3816_3817delAG;c.3836+1G>A;c.3911delA;c.3911dupA;c.3965delT;c.3980G>A;c.4165_4166delCC;c.4175_4176delTT;c.4197delA;c.4221dupA;c.4260-12A>G;c.4260-1G>T;c.4322_4323dupAA;c.4323delA;c.4342G>C;c.4347+1G>A;c.4348G>T;c.4353G>T;c.4456delT;c.4459C>T;c.4481+1G>C;c.4481+2T>G;c.4529dupA

Rhizomelic chondrodysplasia punctata, type 3

Descripción enfermedad:
Rhizomelic chondrodysplasia punctata, type 3 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the AGPS gene located on chromosomal region 2q31.2. The age of onset is neonatal/infantile. This disease is characterized by shortness of the femur and humerus, vertebral disorders, cataract, cutaneous lesions and severe intellectual deficit. The prevalence is 1:100,000-9:100,000.

c.926C>T;c.1256G>A;c.1406T>C;c.1703C>T

Hyperoxaluria, primary, type 1

Descripción enfermedad:
Primary hyperoxaluria, type 1 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the AGXT gene located on chromosomal region 2q37.3. The age of onset is variable. This disease is characterized by variable clinical presentation, ranging from occasional symptomatic nephrolithiasis to nephrocalcinosis and end-stage renal disease with systemic involvement. The prevalence is 1:1,000,000-9:1,000,000.

c.2_3delTGinsAT;c.2T>C;c.3G>T;c.32_33delCC;c.33delC;c.33dupC;c.32C>G;c.74T>G;c.77T>C;c.83delC;c.106C>T;c.107G>A;c.116_117dupCA;c.126delG;c.126dupG;c.121G>A;c.122G>A;c.122G>T;c.125G>A;c.130C>T;c.139G>A;c.166-2A>G;c.166-1G>A;c.167T>A;c.187G>C;c.198C>G;c.205C>T;c.209C>A;c.215dupA;c.221_227dupTCACACT;c.242C>A;c.242C>T;c.244G>C;c.245G>A;c.248A>G;c.276delT;c.283_285dupGAG;c.283G>A;c.322T>C;c.327delG;c.323G>A;c.324G>T;c.326G>T;c.331C>T;c.332G>A;c.335C>A;c.349G>T;c.353G>A;c.358+1G>T;c.358+2T>G;c.364C>T;c.406_410dupCTGCA;c.409C>T;c.423G>T;c.423+1G>A;c.424-2A>G;c.445delG;c.447_454delGCTGCTGT;c.449T>C;c.454T>A;c.460delA;c.466G>A;c.473C>A;c.473C>T;c.481G>A;c.481G>C;c.481G>T;c.497T>C;c.508G>A;c.518G>A;c.519C>A;c.524+2T>A;c.525-1G>A;c.533G>A;c.547G>A;c.560C>T;c.570delG;c.568G>A;c.577delC;c.577dupC;c.583A>C;c.584T>G;c.596-2A>G;c.603C>A;c.605T>A;c.612C>A;c.613T>C;c.614C>A;c.614C>T;c.642_645delTCCA;c.646G>A;c.661T>C;c.673_676delAAGG;c.679_680+2delAAGT;c.680+1G>A;c.680+1G>C;c.680+2T>A;c.681-1G>T;c.697C>T;c.698G>A;c.698G>T;c.725dupT;c.727G>C;c.731T>C;c.737G>A;c.738G>A;c.744delC;c.752G>A;c.753G>A;c.757T>C;c.776+1G>A;c.776+1G>C;c.776+2T>G;c.777-2A>G;c.777-1G>C;c.798_802delCATCAinsACAATCTCAG;c.806T>C;c.823_824dupAG;c.822G>C;c.834delC;c.844C>T;c.846G>C;c.846+1G>A;c.846+1G>T;c.847-1G>C;c.851T>C;c.853G>T;c.891T>G;c.893T>C;c.907C>T;c.919delC;c.922C>T;c.942+1G>T;c.943-1G>A;c.943-1G>T;c.956C>T;c.959_960delCA;c.971_972delTG;c.976delG;c.996G>A;c.997A>T;c.1014C>G;c.1045G>A;c.1071+1G>A;c.1076T>C;c.1079G>A;c.1079G>C;c.1102G>A;c.1125_1126delCG;c.1151T>C

Joubert syndrome, type 3

Descripción enfermedad:
Joubert syndrome, type 3 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the AHI1 gene located on chromosomal region 6q23.3. The age of onset is variable. This disease is characterized by the neurological features of Joubert syndrome (neonatal hypotonia, developmental delay, mild to severe intellectrual disability, ataxia, and abnormal eye movements including oculomotor apraxia and primary position nystagmus) associated with retinal dystrophy.

c.3263_3264delGG;c.2988delA;c.2609G>A;c.2598_2604delAGTGTAT;c.2569_2570insAG;c.2495T>G;c.2493-2A>G;c.2368_2369insT;c.2297G>A;c.2295dupA;c.2212C>T;c.2187_2196delGAGAGAAGAT;c.2174G>A;c.2172delA;c.2173T>C;c.2168G>A;c.2156A>G;c.2098_2099dupGT;c.2087A>G;c.2036+1G>T;c.2023G>A;c.2012C>T;c.1997A>T;c.1917T>A;c.1897_1898dupGG;c.1861G>T;c.1765C>T;c.1626+1G>A;c.1614delA;c.1516C>T;c.1484G>A;c.1303C>T;c.1267C>T;c.1260G>A;c.1205delC;c.1152-2A>G;c.1052G>T;c.1051C>T;c.985C>T;c.910dupA;c.736A>T;c.662C>G

Autoimmune polyendocrinopathy syndrome type 1

Descripción enfermedad:
Autoimmune polyendocrinopathy syndrome (APS) type 1, also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is characterized by the presence of 2 of 3 major clinical symptoms: Addison disease, and/or hypoparathyroidism, and/or chronic mucocutaneous candidiasis (Neufeld et al., 1981).

c.1A>G;c.1A>T;c.62C>T;c.83T>C;c.132+1_132+3delGTGinsCT;c.157G>T;c.199_202delCTGAinsTGG;c.205_208dupCAGG;c.232T>C;c.233G>A;c.239T>G;c.247A>G;c.254A>G;c.255C>A;c.260delT;c.274C>T;c.319_321delAGCinsTG;c.328delC;c.415C>T;c.457_458delAGinsC;c.463+2T>C;c.464-2A>T;c.469C>T;c.510_522dupAGAGCAGCAGCGC;c.517C>T;c.652+1G>T;c.652+2T>C;c.682G>T;c.769C>T;c.789delC;c.798+1G>A;c.798+1G>C;c.798+1G>T;c.809_810delAG;c.823delC;c.931delT;c.932G>A;c.958delC;c.967_979delCTGTCCCCTCCGC;c.977delC;c.1066dupC;c.1084delG;c.1095+1G>A;c.1096-1G>A;c.1103dupC;c.1116_1117delGG;c.1163_1164insA;c.1193delC;c.1249dupC;c.1265delC;c.1278+1delG;c.1279-2A>G;c.1365G>A;c.1513delG;c.1566+2T>A;c.1567-2A>G;c.1616C>T;c.1638A>T

Sjogren-Larsson syndrome

Descripción enfermedad:
Sjogren-Larsson syndrome is an autosomal recessive, early childhood-onset disorder characterized by ichthyosis, mental retardation, spastic paraparesis, macular dystrophy, and leukoencephalopathy. It is caused by deficiency of fatty aldehyde dehydrogenase (FALDH) (Lossos et al., 2006).

c.28C>T;c.73C>T;c.103C>T;c.153+2T>G;c.154_155delAG;c.191T>A;c.231delA;c.234G>A;c.281dupA;c.374_378delCCATC;c.386-2A>T;c.471+1delG;c.471+2T>G;c.472-2A>G;c.521delT;c.551C>T;c.574dupA;c.577delG;c.623T>C;c.641G>A;c.733G>A;c.769dupA;c.798+1delG;c.798+1_798+6delGTTTGT;c.798+1G>A;c.809delG;c.824_825delAG;c.835T>A;c.901_903delGCTinsCC;c.943C>T;c.979delG;c.1069A>T;c.1094C>T;c.1100delA;c.1108-2A>G;c.1108-1G>A;c.1108-1G>C;c.1108-1G>T;c.1157A>G;c.1202G>A;c.1207+1G>A;c.1212delC;c.1277T>G;c.1291_1292delAA;c.1297_1298delGA;c.1302dupT;c.1307_1311dupACAAA;c.1367T>A;c.1443+1G>A;c.*42-1G>T

Fructose intolerance, hereditary

Descripción enfermedad:
Hereditary fructose intolerance follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ALDOB gene located on chromosomal region 9q21.3-q22.2. The age of onset is neonatal/infantile. This disease is characterized by severe abdominal pain, vomiting, and hypoglycemia following ingestion of fructose or other sugars metabolised through fructose-1-phosphate. The prevalence is 1:100,000-9:100,000.

c.1067C>A;c.1013C>T;c.1005C>G;c.940dupT;c.941G>A;c.911G>A;c.888G>A;c.865delC;c.800-2A>C;c.720C>A;c.625-1G>A;c.625-2A>G;c.612T>A;c.546delA;c.524C>A;c.522C>G;c.448G>C;c.444G>A;c.442T>C;c.420delA;c.380-1G>A;c.380-2A>G;c.379+1G>A;c.360_363delCAAA;c.325-1G>A;c.324+2T>A;c.324+1G>A;c.178C>T;c.113-1_115delGGTA;c.112+1delG;c.10C>T;c.2T>C;c.-11+1G>C

Congenital disorder of glycosylation, type 1K

Descripción enfermedad:
Congenital disorder of glycosylation type 1K follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ALG1 gene located on chromosomal region 16p13.3. The age of onset is neonatal/infantile. This disease is characterized by psychomotor delay, seizures, microcephaly and coagulation anomalies. The prevalence is <1:1,000,000.

c.15C>A;c.149A>G;c.304C>T;c.434G>A;c.450C>G;c.773C>T;c.823G>T;c.863-2A>G;c.901+1G>A;c.1079C>T;c.1129A>G;c.1187+1G>A;c.1187+3A>G;c.1250_1251insTG

Congenital disorder of glycosylation, type 1C

Descripción enfermedad:
Congenital disorder of glycosylation type 1C follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ALG6 gene located on chromosomal region 1p31.3. The age of onset is neonatal/infantile. This disease is characterized by psychomotor delay and muscular hypotonia, and possible coagulation anomalies, hormonal abnormalities and seizures. The prevalence is <1:1,000,000.

c.171T>A;c.257+5G>A;c.316C>T;c.680G>A;c.680+2T>G;c.897_899delAAT;c.908_910delGTT;c.998C>T;c.1432T>C

Alström syndrome

Descripción enfermedad:
Alström syndrome follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ALMS1 gene located on chromosomal region 2p13.1. The age of onset is neonatal/infantile. This disease is characterized by cone-rod dystrophy, hearing loss, obesity, insulin resistance and hyperinsulinemia, type 2 diabetes mellitus, dilated cardiomyopathy and progressive hepatic and renal dysfunction. The prevalence is 1:10,000-1:1,000,000.

c.355C>T;c.359_360delTA;c.427C>T;c.709G>T;c.925_926insT;c.1051C>T;c.1196_1202delCACAGGA;c.1229_1230delAT;c.1237+2T>C;c.1432+2_1432+15delTACGTAGAAAAAGG;c.1557delG;c.1607_1608delTC;c.1668delT;c.1729delA;c.1788_1795dupGGCTTTGA;c.1894C>T;c.2127_2131delAGTAC;c.2135_2136delCT;c.2173dupT;c.2218dupA;c.2290_2293delTCAC;c.2323C>T;c.2723C>G;c.2749dupT;c.2787dupA;c.2816T>A;c.3013dupA;c.3294_3295delAA;c.3334delG;c.3486_3495delTATACCTGAA;c.3684_3685delTG;c.3778G>T;c.3870_3871delGA;c.4150dupA;c.4246delC;c.4290_4293delCACA;c.4422delC;c.4642dupA;c.4911_4914delTAAA;c.5139T>G;c.5173dupC;c.5193_5194delTC;c.5412delC;c.5459delC;c.5584C>T;c.5619delA;c.5624dupT;c.5857delG;c.5883delA;c.5920delG;c.5975_5976delAA;c.6163_6164dupAT;c.6430C>T;c.6480_6483delAACT;c.6565_6568delTCAC;c.6567_6570dupACAT;c.6584delA;c.6794T>A;c.6834delT;c.6895delG;c.6954_6957delACAG;c.7241C>A;c.7298_7299delAG;c.7369_7370delGA;c.7370_7373delATAG;c.7385_7389dupAGGGT;c.7824delC;c.8002C>T;c.8130delT;c.8138_8145delCCATCACT;c.8149dupT;c.8158C>T;c.8346_8349delAGAA;c.8377C>T;c.8383C>T;c.8388dupA;c.8411dupC;c.8753_8756delCTTC;c.8787dupT;c.9148_9149delCT;c.9427dupA;c.9535C>T;c.9614_9618delCAGAA;c.9757_9758dupAC;c.9812_9825delGTAGTACCAAGATG;c.9894dupC;c.10128dupA;c.10284_10285delTA;c.10297delCinsGA;c.10477C>T;c.10543C>T;c.10769delC;c.10784_10785delTG;c.10794_10797delTGAA;c.10819C>T;c.10825_10826delAG;c.10879C>T;c.10939G>T;c.10986G>A;c.11080delA;c.11201C>A;c.11310_11313delAGAG;c.11379delT;c.11443C>T;c.11453dupA;c.11612_11613delCT;c.11613dupT;c.11645_11646insGTTA;c.11697delA;c.11711_11714delTTGG;c.11781G>A;c.11806dupA;c.11870-2A>T;c.11988G>A;c.12080_12083delTACT;c.12101_12102delCA;c.12299_12302delTCCT;c.12439C>T;c.12445C>T

Hypophosphatasia, childhood/infantile

Descripción enfermedad:
Childhood-onset hypophosphatasia follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ALPL gene located on chromosomal region 1p36.12. The age of onset is infantile. This inborn error of metabolism is characterized clinically by defective bone mineralization ranging from stillbirth without mineralized bone to pathologic fractures of the lower extremities in later adulthood; biochemically is characterized by deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase.

c.18delA;c.46_49delAACT;c.61+2T>G;c.87G>A;c.88C>T;c.98C>T;c.114delA;c.129delT;c.130C>T;c.211C>T;c.212G>C;c.215T>C;c.297+2T>A;c.323C>T;c.346G>A;c.392delG;c.400_401delACinsCA;c.407G>A;c.427delC;c.522delC;c.526G>A;c.535G>A;c.542C>T;c.550C>T;c.571G>A;c.620A>C;c.648+1G>A;c.662dupG;c.667C>T;c.668G>A;c.791A>G;c.809G>A;c.814C>T;c.815G>A;c.841delC;c.862+1G>A;c.871G>A;c.881A>C;c.891C>A;c.892G>A;c.903delG;c.928_929delTC;c.963delG;c.979T>C;c.997+2T>G;c.998-2A>G;c.1001G>A;c.1039C>T;c.1088_1091dupGCAG;c.1114_1115delCT;c.1133A>T;c.1144G>A;c.1171C>T;c.1181_1182delCT;c.1216_1219delGACA;c.1250A>G;c.1306T>C;c.1363G>A;c.1366G>A;c.1559delT

Glycine encephalopathy

Descripción enfermedad:
Glycine encephalopathy follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the AMT and GLDC genes located on chromosomal regions 3p21.31 and 9p24.1 respectively. The age of onset is neonatal/infantile. This disease is characterized by lethargy or even coma, hypotonia, hiccups, myoclonic jerks, and breathing/swallowing disorders, with subsequent intellectual deficit, spasticity and intractable seizures. The prevalence is 1:1,000,000-9:1,000,000.

c.1033+2T>C;c.982_983delGCinsT;c.982delG;c.959G>A;c.878-1G>A;c.870G>A;c.849dupT;c.826G>C;c.806G>A;c.696+2T>A;c.696+1G>A;c.674A>G;c.574C>T;c.535delC;c.496C>T;c.471+2T>C;c.434A>T;c.348_349delGT;c.259-1G>C;c.230C>T;c.164G>A;c.144_148delAATGG;c.148delG;c.125A>G;c.61delG;c.59delC;c.16delA

Androgen insensitivity syndrome, complete

Descripción enfermedad:
The complete androgen insensitivity syndrome (CAIS) follows an X-linked pattern of inheritance and is caused by pathogenic variants in the AR gene located on chromosomal region Xq12. Affected males have female external genitalia, female breast development, blind vagina, absent uterus and female adnexa, and abdominal or inguinal testes, despite a normal male 46,XY karyotype. There is unresponsiveness to age-appropriate levels of androgens. There is also a partial androgen insensitivity syndrome (PAIS; OMIM 312300) caused by mutations in the AR gene, called Reifenstein syndrome, which results in hypospadias and micropenis with gynecomastia. Note: A specific type of mutation in the AR gene (a CAG repeat expansion) also cause a rare condition known as Spinal and bulbar muscular atrophy or Kennedy disease; this mutation is not tested by this carrier test.

c.178C>T;c.217C>T;c.268C>T;c.340C>T;c.393C>A;c.521T>G;c.796dupG;c.865G>T;c.1185C>A;c.1720G>C;c.1732G>A;c.1739G>A;c.1739G>T;c.1748T>A;c.1768+2T>C;c.1771A>T;c.1789G>A;c.1804T>G;c.1822C>T;c.1823G>A;c.1826G>A;c.1847G>A;c.1886-1G>A;c.1888delC;c.1888C>T;c.1952delG;c.2033T>C;c.2069A>C;c.2103G>T;c.2104C>T;c.2105T>A;c.2117A>G;c.2123T>G;c.2137C>A;c.2137C>T;c.2157G>A;c.2164G>A;c.2191G>A;c.2222C>G;c.2231G>A;c.2231G>T;c.2248A>G;c.2257C>T;c.2258G>A;c.2258G>T;c.2281_2287delAGGATGCinsTTCGCCCCTGA;c.2291A>G;c.2296G>A;c.2297C>A;c.2301delT;c.2314A>C;c.2318+1G>C;c.2323C>T;c.2324G>A;c.2343G>A;c.2343G>T;c.2359C>T;c.2362A>G;c.2391G>A;c.2395C>G;c.2420G>A;c.2423T>C;c.2437C>T;c.2438T>C;c.2450-1G>A;c.2504A>G;c.2521C>T;c.2522G>A;c.2562_2563delAA;c.2566C>T;c.2567G>A;c.2567G>T;c.2571C>G;c.2596T>C;c.2599G>A;c.2599G>T;c.2610T>G;c.2613delG;c.2623C>T;c.2632A>G;c.2650A>T;c.2668G>A;c.2668G>C;c.2708A>G

Argininemia (arginase deficiency)

Descripción enfermedad:
Argininemia, also known as arginase deficiency, follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ARG1 gene located on chromosomal region 6q23. The age of onset is neonatal/infantile. This disease is characterized by variable degrees of hyperammonemia, developing from about 3 years of age, and leading to progressive loss of developmental milestones and spasticity in the absence of treatment. The prevalence is 1:350,000-1:1,000,000.

c.2T>C;c.32T>C;c.57+1G>A;c.58-2A>C;c.61C>T;c.129delA;c.130+1G>T;c.296dupG;c.389G>A;c.437G>T;c.490-2A>G;c.490-1G>C;c.717delT;c.727G>A;c.727G>C;c.811G>T;c.868delC;c.895C>T

Metachromatic leukodystrophy

Descripción enfermedad:
Metachromatic leukodystrophy follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ARSA gene located on chromosomal region 22q13.33. The age of onset is variable. This disease is characterized by hypotonia, walking difficulties, optic atrophy and motor regression preceding mental impairment in the late infantile form, arrested intellectual development, followed by motor regression, epileptic seizures and ataxia in the juvenile form, and motor or psychiatric disorders, but with slow progression in the adult form. The incidence is 0.5:5,000-1:50,000 and the prevalence is 1:10,000 -5/10,000.

c.1489_1492dupCCCC;c.1492dupC;c.1462C>T;c.1408_1418delGCAGCTGTGAC;c.1401_1411delGTTAGACGCAG;c.1344dupC;c.1337delG;c.1283C>T;c.1279C>A;c.1274A>G;c.1264delC;c.1241delC;c.1232C>T;c.1210+1G>A;c.1210+1G>T;c.1175G>A;c.1174C>T;c.1150G>A;c.1136C>T;c.1125_1126delCT;c.1114C>T;c.1108-2A>G;c.1107+1delG;c.1036delG;c.1010A>T;c.991G>T;c.986C>T;c.980-2A>C;c.979_979+3delGGTC;c.979+1G>A;c.979G>A;c.960G>A;c.938G>A;c.937C>T;c.931G>A;c.929delG;c.905G>T;c.899T>C;c.891delC;c.890C>A;c.883G>A;c.877C>T;c.869G>A;c.868C>T;c.862A>C;c.854+1G>A;c.854+1G>T;c.827C>T;c.769G>C;c.763G>A;c.758dupT;c.746T>C;c.739G>A;c.737G>A;c.697C>A;c.674_675dupAT;c.641C>T;c.622delC;c.583delT;c.582delC;c.545delC;c.545C>G;c.542dupT;c.542T>G;c.526C>T;c.495_501delGCCGGCC;c.494dupC;c.474C>A;c.470C>G;c.467G>A;c.466-2A>G;c.465+2T>A;c.465+1G>A;c.421C>T;c.418delC;c.418dupC;c.410T>C;c.346C>T;c.304delC;c.302delG;c.302G>A;c.293C>T;c.263G>A;c.257G>A;c.256C>T;c.240dupC;c.229G>C;c.227_228insTA;c.225-2A>G;c.224+1G>A;c.211_212delTG;c.206_209delCTCT;c.195delC;c.185_186dupCA;c.109_116delGACCTGGG;c.98T>C;c.34delG

Mucopolysaccharidosis, type 6 (Maroteaux-Lamy syndrome)

Descripción enfermedad:
Mucopolysaccharidosis type 6, also known as Maroteaux-Lamy syndrome, follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ARSB gene located on chromosomal region 5q14.1. The age of onset is infantile. This lysosomal storage disorder resulting from a deficiency of arylsulfatase B is characterized by educed pulmonary function, hepatosplenomegaly, hearing loss, sleep apnea, corneal clouding, carpal tunnel disease and occasionally central nervous system findings may include cervical cord compression caused by cervical spinal instability, meningeal thickening and/or bony stenosis, communicating hydrocephalus, optic nerve atrophy and blindness. The prevalence is 1:250,000-1:600,000 newborns.

c.1577delC;c.1539C>G;c.1507C>T;c.1482delC;c.1475delC;c.1438dupG;c.1394C>G;c.1391C>A;c.1366C>T;c.1350G>C;c.1336+2T>G;c.1279delA;c.1261G>T;c.1214G>A;c.1214-2A>G;c.1208delC;c.1208C>G;c.1197C>G;c.1178A>C;c.1161dupC;c.1143-1G>C;c.1143-8T>G;c.1142+2T>A;c.1142+2T>C;c.1142+1G>T;c.1130G>A;c.1059G>A;c.1036delG;c.979C>T;c.971G>T;c.966G>A;c.944G>A;c.943C>T;c.937C>G;c.936G>T;c.921delA;c.883_884dupTT;c.785dupA;c.765T>A;c.750_754delATACTinsCCTGAAGTCAAG;c.753C>G;c.743delC;c.691-1G>A;c.659_660delTA;c.630_636delTTCAACA;c.629A>G;c.589C>T;c.574T>C;c.571C>T;c.533A>T;c.532C>G;c.498delT;c.479G>A;c.478C>T;c.454C>T;c.438G>A;c.430G>A;c.427delG;c.375dupT;c.349T>C;c.328C>T;c.289C>T;c.284G>A;c.262C>T;c.253T>C;c.245delT;c.245T>G;c.237_243delGGTGCTC;c.238delG;c.208_215delCCGCACCT;c.215T>G;c.207_213dupGCCGCAC;c.116_123delCCGGGGCC

Chondrodysplasia punctata, brachytelephalangic

Descripción enfermedad:
X-linked chondrodysplasia punctata, brachytelephalangic follows an X-linked pattern of inheritance and is caused by pathogenic variants in the ARSE gene located on chromosomal region Xp22.33. The age of onset is neonatal. This is a disorder of cartilage and bone development that occurs almost exclusively in males. Include short stature and unusually short fingertips and ends of the toes. This condition is also associated with distinctive facial features, particularly a flattened-appearing nose with crescent-shaped nostrils and a flat nasal bridge. People with X-linked chondrodysplasia punctata 1 typically have normal intelligence and a normal life expectancy. However, some affected individuals have had serious or life-threatening complications including abnormal thickening (stenosis) of the cartilage that makes up the airways, which restricts breathing. Also, abnormalities of spinal bones in the neck can lead to pinching (compression) of the spinal cord, which can cause pain, numbness, and weakness. Other, less common features of X-linked chondrodysplasia punctata 1 include delayed development, hearing loss, vision abnormalities, and heart defects. The prevalence is 1:500,000.

c.1818G>A;c.1807C>T;c.1550G>A;c.1517C>T;c.1504delG;c.1462G>A;c.1375G>A;c.485G>T;c.424G>A;c.407G>A;c.407G>C;c.194T>G;c.99-1G>A

Argininosuccinic aciduria

Descripción enfermedad:
Argininosuccinic aciduria follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ASL gene located on chromosomal region 7q11.21. The age of onset is infantile. This disease is characterized by severe hyperammonemic coma, hypotonia, growth failure, anorexia and chronic vomiting or behavioral disorders during childhood, and hyperammonemic coma or behavioral disorders that simulate psychiatric disorders later in life. The prevalence is 1:70,000 newborns.

c.13-1G>C;c.35G>A;c.175G>A;c.257A>C;c.283C>T;c.291+1G>T;c.292delG;c.292G>T;c.299T>C;c.332G>A;c.337C>T;c.346C>T;c.446+1G>A;c.446+2T>C;c.447-1G>A;c.461T>C;c.524+2T>G;c.525-2A>T;c.532G>A;c.539T>G;c.544C>T;c.545G>A;c.575_580dupAGCGGA;c.578G>A;c.602+1G>A;c.637C>T;c.649C>T;c.735G>A;c.762C>A;c.765dupG;c.857A>G;c.889C>T;c.918+5G>A;c.973_976delTTAC;c.978G>C;c.1045_1057delGTCATCTCTACGC;c.1060C>T;c.1122dupC;c.1135C>T;c.1144-2A>G;c.1153C>T;c.1249_1250+12delAGGTACGGCCCATC;c.1255_1256delCT;c.1360C>T;c.1369dupG

Canavan disease

Descripción enfermedad:
Canavan disease follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ASPA gene located on chromosomal region 17p13.3. The age of onset is neonatal/infantile. This disease is characterized by a variable spectrum between severe forms with leukodystrophy, macrocephaly and severe developmental delay, and a very rare mild/juvenile form characterized by mild developmental delay. The prevalence is 1:6,400- 1:13,500 in Askenazis Jewis.

c.2T>C;c.32delT;c.79G>A;c.212G>A;c.236+1G>A;c.237-2A>T;c.237-1G>A;c.237-1G>T;c.244dupA;c.244_245delAT;c.245delT;c.340G>T;c.382delC;c.433-2A>G;c.514_515dupAA;c.527-2A>C;c.631G>T;c.634+1G>T;c.640G>T;c.650_651delCC;c.654C>A;c.679_682delGAGA;c.697delC;c.693C>A;c.745-2A>G;c.745-1G>A;c.770C>G;c.827_828delGT;c.854A>C;c.859G>A;c.876_879delAGAA;c.914C>A;c.924delT

Citrullinemia, type 1

Descripción enfermedad:
Citrullinemia, type 1 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ASS1 gene located on chromosomal region 9q34.1. The age of onset is variable. This disease is characterized by hyperammonemia, progressive lethargy, poor feeding and vomiting in the neonatal form and by variable hyperammonemia in the later-onset form. The prevalence is 1:100,000-9:100,000.

c.-4C>T;c.40G>A;c.175-1G>A;c.226delG;c.256C>T;c.257G>A;c.291C>A;c.349G>A;c.412C>T;c.420+1G>A;c.421-2A>G;c.450_451delCT;c.470G>A;c.496-2A>G;c.535T>C;c.539G>A;c.566+1G>T;c.567-1G>T;c.571G>A;c.688+1_688+5delGTATG;c.689G>C;c.773+1G>A;c.787G>A;c.793C>T;c.794G>A;c.805G>A;c.814C>T;c.823G>T;c.835C>T;c.836G>A;c.838+1G>T;c.847G>A;c.851C>T;c.892delG;c.910C>T;c.919C>T;c.931C>T;c.951delT;c.970G>A;c.970+1G>A;c.970+5G>A;c.971-1G>A;c.978delG;c.1030C>T;c.1064delA;c.1069C>T;c.1085G>T;c.1087C>T;c.1088G>A;c.1127+1G>A;c.1138C>T;c.1139delA;c.1168G>A;c.1194-1G>C

Ataxia-telangiectasia

Descripción enfermedad:
Ataxia-telangiectasia (AT) is an autosomal recessive disorder characterized by cerebellar ataxia, telangiectases, immune defects, and a predisposition to malignancy. Chromosomal breakage is a feature. AT cells are abnormally sensitive to killing by ionizing radiation (IR), and abnormally resistant to inhibition of DNA synthesis by ionizing radiation. The latter trait has been used to identify complementation groups for the classic form of the disease (Jaspers et al., 1988). At least 4 of these (A, C, D, and E) map to chromosome 11q23 (Sanal et al., 1990) and are associated with mutations in the ATM gene.

c.-30-1G>T;c.1A>G;c.2T>C;c.3G>A;c.8delT;c.15dupT;c.43delC;c.67C>T;c.72+1G>A;c.73-1G>A;c.103C>T;c.119_122delTTAA;c.138_141delTTCA;c.140C>G;c.151C>T;c.154G>T;c.157A>T;c.170G>A;c.185+1G>A;c.186-1G>A;c.192delA;c.193C>T;c.205C>T;c.217_218delGA;c.237delA;c.283C>T;c.289delA;c.299T>A;c.331+1G>A;c.331+2T>G;c.331+5G>A;c.332-1G>A;c.364_368delAATTA;c.362T>A;c.368delA;c.378delT;c.381delA;c.387delA;c.392C>A;c.392C>G;c.432dupA;c.450_453delTTCT;c.471T>A;c.478_482delTCTCA;c.484C>T;c.496G>T;c.496+1G>A;c.496+5G>A;c.497-1G>C;c.513C>G;c.538C>T;c.549_550delTA;c.557T>G;c.561_562delGGinsT;c.564delT;c.588delA;c.597T>A;c.601C>T;c.606_609delTGAC;c.640delT;c.642delC;c.652C>T;c.662+1G>A;c.663-2A>G;c.664C>T;c.680delC;c.680C>G;c.689delA;c.710delC;c.717_720delCCTC;c.741dupT;c.742C>T;c.748C>T;c.756_757delTG;c.785T>A;c.790delT;c.802C>T;c.824delT;c.829G>T;c.850C>T;c.875C>T;c.877A>T;c.901+1G>A;c.901+1G>C;c.901+1G>T;c.902-1G>T;c.967A>G;c.977_978delTA;c.992delA;c.1003G>T;c.1017delT;c.1027_1030delGAAA;c.1053dupT;c.1058_1059delGT;c.1063C>T;c.1065+1G>C;c.1065+1G>T;c.1066-2A>C;c.1066-2A>T;c.1066-1G>A;c.1066-1G>T;c.1093G>T;c.1109dupA;c.1110C>G;c.1120C>T;c.1126_1127delGA;c.1126G>T;c.1139_1142dupACAG;c.1158delG;c.1179_1180delGG;c.1178G>A;c.1192delG;c.1208C>A;c.1212_1213delGA;c.1215delT;c.1221dupT;c.1235+1delG;c.1235G>A;c.1235+1G>A;c.1236-3_1236-2delTA;c.1236-2A>G;c.1236-2A>T;c.1236-1G>A;c.1240C>T;c.1249delA;c.1264A>T;c.1285_1288delAACT;c.1284_1291delTAACTGTG;c.1290_1291delTG;c.1305delA;c.1329delA;c.1333delC;c.1339C>T;c.1348delG;c.1348G>T;c.1355delC;c.1368dupA;c.1369C>T;c.1394_1395delGT;c.1396C>T;c.1402_1403delAA;c.1424C>G;c.1435_1436delGA;c.1439_1448delTATTAAAACT;c.1442T>G;c.1446delA;c.1463G>A;c.1495C>T;c.1501C>T;c.1514_1515delTT;c.1524delT;c.1537C>T;c.1547T>A;c.1547T>C;c.1547T>G;c.1564_1565delGA;c.1573A>T;c.1597_1600dupAGAC;c.1607+1G>T;c.1608-1G>A;c.1608-1G>C;c.1655delC;c.1658delG;c.1660delA;c.1692T>A;c.1697_1706delTAAATAGAAG;c.1737G>A;c.1740_1741delCT;c.1741_1742delTT;c.1753_1756delTTAG;c.1768G>T;c.1803-2A>G;c.1856delA;c.1880dupT;c.1898+1G>A;c.1898+1G>T;c.1898+2T>G;c.1899-1G>A;c.1915_1916insT;c.1920_1923delAGAA;c.1918A>T;c.1924G>T;c.1931C>A;c.1939G>T;c.1960C>T;c.2023C>T;c.2050C>T;c.2080_2081delCT;c.2098C>T;c.2113delT;c.2115C>G;c.2119_2123delTCTGA;c.2124+1G>T;c.2125-2A>C;c.2125-1G>A;c.2125delA;c.2129delC;c.2135C>G;c.2165dupT;c.2167_2173delGTGGGTG;c.2193C>A;c.2250+1G>A;c.2250+2T>C;c.2251-10T>G;c.2251-1G>C;c.2272G>T;c.2284_2285delCT;c.2286_2287delGT;c.2295delT;c.2308G>T;c.2376+1G>A;c.2376+1G>C;c.2376+1G>T;c.2377-2A>G;c.2413C>T;c.2426C>A;c.2465T>A;c.2466+1delG;c.2466+1G>A;c.2466+2T>A;c.2466+2T>G;c.2467-2A>C;c.2467-2A>T;c.2467-1G>A;c.2483delA;c.2494dupC;c.2497G>T;c.2500G>T;c.2502dupA;c.2521delG;c.2542G>T;c.2548G>T;c.2554C>T;c.2564dupT;c.2572_2575delTTTA;c.2583C>A;c.2606_2607delCA;c.2620G>T;c.2638+1delG;c.2638+2T>C;c.2654_2656delTAGinsAA;c.2654T>G;c.2662G>T;c.2672C>G;c.2677C>T;c.2693T>G;c.2720_2723delGTGT;c.2727delT;c.2730_2731insAG;c.2734C>T;c.2754delT;c.2775delG;c.2789T>G;c.2806_2809dupCTAG;c.2838+1G>T;c.2839-3_2839delTAGTinsGATACTA;c.2839-2A>G;c.2849T>G;c.2880delC;c.2877C>G;c.2882delT;c.2897_2899delTTCinsGCCAA;c.2902G>T;c.2912_2916delAACCA;c.2921+1G>A;c.2921+1G>C;c.2921+1G>T;c.2922-1G>T;c.2965delA;c.2985_2988delTCAT;c.2999dupA;c.3025G>T;c.3038dupA;c.3043C>T;c.3049C>T;c.3068delG;c.3077G>A;c.3077+1G>A;c.3078-1G>A;c.3078G>A;c.3085dupA;c.3102T>G;c.3154-2A>G;c.3154-1G>A;c.3167C>A;c.3206delC;c.3214G>T;c.3218dupT;c.3231dupT;c.3242_3245delATCA;c.3245_3247delATCinsTGAT;c.3252_3259delAGTTCGCA;c.3279_3282delCAAT;c.3279_3280insT;c.3284G>A;c.3284+1G>A;c.3284+1G>C;c.3292delC;c.3304G>T;c.3315dupC;c.3320_3323delTACT;c.3320T>A;c.3335dupC;c.3340A>T;c.3351_3354delAACA;c.3349C>T;c.3369delA;c.3372C>G;c.3381_3384delTCAG;c.3382C>T;c.3388G>T;c.3402+2T>C;c.3403-1G>A;c.3435_3436delTGinsA;c.3436G>T;c.3450_3454delAAAAT;c.3451A>T;c.3510dupA;c.3511C>T;c.3526delC;c.3532A>T;c.3539_3540delTG;c.3541A>T;c.3576G>A;c.3576+1G>A;c.3576+1G>T;c.3577-1G>C;c.3602_3603delTT;c.3603delT;c.3617_3621delTAGAAinsG;c.3619G>T;c.3626_3627delTT;c.3627delT;c.3631delG;c.3663G>A;c.3673C>T;c.3693_3697delATCTT;c.3704delC;c.3712_3716delTTATT;c.3747-2A>G;c.3747-1G>A;c.3747-1G>C;c.3754_3756delTATinsCA;c.3756T>A;c.3760delG;c.3780dupG;c.3802delG;c.3836G>A;c.3841delA;c.3848T>C;c.3850delA;c.3852delA;c.3865A>T;c.3880dupA;c.3894dupT;c.3895delG;c.3931C>T;c.3939_3940delGA;c.3935dupG;c.3980T>G;c.3990delA;c.3993+1G>A;c.3993+1G>T;c.3994-2A>C;c.3994-2A>G;c.3994-1G>T;c.4019_4029delTACCAGAGATT;c.4036G>T;c.4052delT;c.4052T>A;c.4081C>T;c.4084_4085delAG;c.4098_4099delTG;c.4104_4105delTT;c.4106C>A;c.4109+1G>T;c.4110-1G>A;c.4143dupT;c.4148C>A;c.4198A>T;c.4227delC;c.4236+1G>T;c.4246C>T;c.4303A>T;c.4318A>T;c.4330_4333delCTGTinsTAAAATAAA;c.4332_4337delGTTTGTinsTAAAA;c.4344dupA;c.4358_4359delTA;c.4359_4363delAAAAA;c.4370T>G;c.4373delG;c.4394T>C;c.4396C>T;c.4405delA;c.4415T>A;c.4416delG;c.4436+1G>T;c.4436+2T>C;c.4437-1G>A;c.4437-1G>C;c.4451delT;c.4493T>G;c.4507C>T;c.4587T>G;c.4588G>T;c.4609C>T;c.4611+1G>A;c.4612-2A>C;c.4612-1G>A;c.4625dupT;c.4632_4635delCTTA;c.4642_4645delGATA;c.4661delA;c.4664delT;c.4683_4689delTTTAGAT;c.4695delT;c.4732C>T;c.4735C>T;c.4741dupA;c.4774G>T;c.4776+1G>T;c.4776+2T>A;c.4776+2T>C;c.4800_4803delAAGT;c.4804_4805delGT;c.4844delA;c.4842_4843insCT;c.4852C>T;c.4879C>T;c.4906C>T;c.4909+1G>A;c.4909+1G>T;c.4910-2A>T;c.4910-1G>T;c.4938delA;c.4957C>T;c.5005+1G>T;c.5015delG;c.5065C>T;c.5177+1G>A;c.5177+5G>A;c.5178-1G>A;c.5188C>T;c.5192C>G;c.5201_5202insAT;c.5203dupA;c.5209_5210delTT;c.5249G>A;c.5290delC;c.5309C>G;c.5318delA;c.5319+1G>A;c.5319+1G>T;c.5319+2T>C;c.5320-4_5323delCTAGTTTT;c.5320-5_5320-2delTCTA;c.5326G>T;c.5351delA;c.5396delG;c.5405dupA;c.5414G>A;c.5416delA;c.5433T>A;c.5441dupT;c.5443delG;c.5460dupA;c.5496+1G>A;c.5496+1G>T;c.5497-2A>C;c.5497-2A>G;c.5497-1G>A;c.5515C>T;c.5516dupA;c.5549delT;c.5549T>A;c.5554dupC;c.5554C>T;c.5573G>A;c.5623C>T;c.5631_5635delCTCGCinsA;c.5644C>T;c.5653dupA;c.5681_5682delAG;c.5692C>T;c.5697C>A;c.5712dupA;c.5762+1G>A;c.5762+1G>T;c.5763-1050A>G;c.5763-2A>C;c.5763-2A>G;c.5763-2A>T;c.5765delC;c.5771C>A;c.5784dupT;c.5791delGinsCCT;c.5798G>A;c.5870_5871delAT;c.5893_5897delAAAAG;c.5890A>T;c.5894_5900dupAAAGTAT;c.5908C>T;c.5910delA;c.5919-2A>C;c.5919-2A>G;c.5932G>T;c.5935G>T;c.5944C>T;c.5948dupA;c.5959dupT;c.5971G>T;c.5979_5983delTAAAG;c.5982delA;c.6002T>G;c.6006+1G>A;c.6006+1G>C;c.6015dupC;c.6027C>G;c.6040G>T;c.6047A>G;c.6049dupA;c.6056A>G;c.6059delG;c.6080delT;c.6082C>T;c.6095G>A;c.6095+1G>A;c.6095+2T>C;c.6096-2A>G;c.6100C>T;c.6115G>A;c.6115G>T;c.6133delG;c.6154G>A;c.6181C>T;c.6198+1G>A;c.6198+2T>C;c.6199-2A>T;c.6200C>A;c.6222C>A;c.6228delT;c.6239_6240delAT;c.6238T>G;c.6272G>A;c.6289G>T;c.6311G>A;c.6312G>A;c.6326G>A;c.6327G>A;c.6347+1G>A;c.6348-2A>G;c.6348-1G>A;c.6373delC;c.6397C>T;c.6403_6404insCT;c.6404_6405insTT;c.6404dupT;c.6415_6416delGA;c.6433_6445delGAAAGTCTCAAAT;c.6435_6436delAA;c.6436dupA;c.6444dupA;c.6452+1G>T;c.6453-1G>C;c.6482_6483dupGC;c.6490G>T;c.6498_6499delGT;c.6572+1G>A;c.6573-2A>G;c.6586A>T;c.6615G>A;c.6628delC;c.6650_6657delTTAGTTTT;c.6657delT;c.6658C>T;c.6667delA;c.6673dupG;c.6679C>T;c.6725delC;c.6729_6730delAA;c.6752_6755dupTCAC;c.6754delA;c.6776_6777delCT;c.6850delG;c.6866_6867delCT;c.6867dupT;c.6908dupA;c.6913C>T;c.6916_6917delAG;c.6920_6923delTTGC;c.6975+1G>T;c.6976-2A>C;c.6976-2A>G;c.7000_7003delTACA;c.6997dupA;c.7010_7011delGT;c.7032G>A;c.7088delA;c.7089+1G>A;c.7089+1G>T;c.7089+2T>G;c.7091delC;c.7096G>T;c.7141_7151delAATGGAAAAAT;c.7166C>G;c.7181C>T;c.7189C>T;c.7220C>A;c.7240C>T;c.7262_7263delAA;c.7271T>G;c.7279_7284delCTTAGG;c.7293_7294delAA;c.7299_7302delGACA;c.7308-2A>C;c.7308-1G>C;c.7311C>A;c.7327C>T;c.7408T>G;c.7449G>A;c.7456C>T;c.7465_7466delTC;c.7517_7520delGAGA;c.7542T>G;c.7563C>G;c.7570G>C;c.7629_7629+4delTGTAA;c.7629+1G>A;c.7629+2T>C;c.7630-2A>C;c.7630-2A>G;c.7638_7646delTAGAATTTC;c.7665delCinsGTGA;c.7671_7674delGTTT;c.7699_7702delAACA;c.7701_7702delCA;c.7705_7706delGA;c.7708G>T;c.7767delA;c.7768C>T;c.7777C>T;c.7788+1G>T;c.7789-3T>G;c.7792C>T;c.7796delC;c.7838_7839dupGA;c.7875_7876delTGinsGC;c.7880delA;c.7913G>A;c.7921C>T;c.7926A>C;c.7927+1G>C;c.7927+5delG;c.7928-2A>G;c.7928-2A>T;c.7928-1G>A;c.7929delA;c.7951C>T;c.7967T>C;c.7989_7991delTGT;c.7985T>A;c.7988_7991delTTGT;c.7998dupT;c.8010+1delG;c.8011-1G>C;c.8011-1G>T;c.8048_8049delTA;c.8098A>T;c.8103_8104delAA;c.8122G>A;c.8140C>T;c.8146G>T;c.8147T>C;c.8149A>T;c.8152-2A>G;c.8152-1G>A;c.8185C>T;c.8204_8205dupGT;c.8206_8207dupAA;c.8213T>G;c.8218C>T;c.8251_8254delACTA;c.8264_8268delATAAG;c.8265T>G;c.8266A>T;c.8268+1G>T;c.8283_8284delTC;c.8287C>T;c.8288delG;c.8292_8293delTG;c.8293G>A;c.8305_8317delTGGTGCACAGGAA;c.8307G>A;c.8319_8323dupTGTCC;c.8321_8322delTCinsA;c.8325delC;c.8367delAinsTT;c.8371_8374delTACA;c.8373C>A;c.8395_8404delTTTCAGTGCC;c.8397delT;c.8403C>A;c.8418+5_8418+8delGTGA;c.8418+1G>A;c.8418+2T>C;c.8419-2A>G;c.8419-1G>C;c.8419G>T;c.8432delA;c.8432dupA;c.8431A>T;c.8435_8436delCT;c.8440delG;c.8473C>T;c.8476_8477dupAA;c.8480T>G;c.8484delA;c.8494C>T;c.8495G>C;c.8505C>A;c.8514dupA;c.8535G>A;c.8545C>T;c.8546G>C;c.8549T>A;c.8564delG;c.8565_8566delTGinsAA;c.8584+1G>A;c.8584+2T>C;c.8585-2A>C;c.8585-2A>G;c.8585-1G>A;c.8624dupA;c.8641C>T;c.8655dupT;c.8671+1G>T;c.8671+2T>C;c.8672-1G>C;c.8672-1G>T;c.8711A>G;c.8725A>T;c.8737G>T;c.8766dupT;c.8786+1G>A;c.8786+1G>C;c.8786+1G>T;c.8786+2T>A;c.8793T>A;c.8802delC;c.8814_8824delGAGAAACTCTC;c.8818_8821dupAACT;c.8823_8824delTC;c.8833_8834delCT;c.8835_8836delGT;c.8850+1G>A;c.8850+2T>C;c.8851-2A>G;c.8851-1G>T;c.8873_8874delTT;c.8876_8879delACTG;c.8879G>A;c.8880G>A;c.8903T>A;c.8911C>T;c.8942delA;c.8977C>T;c.8987+1G>C;c.8988-2A>C;c.8988-2A>G;c.8988-1G>A;c.8988-1G>C;c.8998C>T;c.9001_9002delAG;c.9019G>T;c.9021dupA;c.9022C>T;c.9023G>A;c.9047_9057delAACTGAAAGGA;c.9064dupG;c.9079dupA;c.9112delC;c.9139C>T;c.9145_9146delTT

Menkes disease; Occipital horn syndrome

Descripción enfermedad:
Menkes disease follows an X-linked pattern of inheritance and is caused by pathogenic variants in the ATP7A gene located on chromosomal region Xq21.1. The age of onset is neonatal/infantile. This disease is characterized by progressive neurodegeneration and marked connective tissue anomalies as well as typical sparse abnormal steely hair. The birth incidence is 1:300,000 in Europe, 1:360,000 in Japan and 1:50,000-1:100,000 in Australia, and the prevalence is 1:100,000 newborns. Mutations in the ATP7A can also cause occipital horn syndrome, which is considered a mild form of Menkes syndrome. Occipital horn syndrome is a rare connective tissue disorder characterized by hyperelastic and bruisable skin, hernias, bladder diverticula, hyperextensible joints, varicosities, and multiple skeletal abnormalities. The disorder is sometimes accompanied by mild neurologic impairment, and bony abnormalities of the occiput are a common feature, giving rise to the name (summary by Das et al., 1995).

c.408_415delCAATCAGA;c.422_423delAG;c.598C>T;c.601C>T;c.876delG;c.1006G>T;c.1020_1024dupGGGGC;c.1205delA;c.1225C>T;c.1355delT;c.1460C>A;c.1537G>T;c.1544-1G>A;c.1639C>T;c.1667_1668delTA;c.1707+1G>A;c.1782C>G;c.1831G>T;c.1870-1G>C;c.1874T>G;c.1885G>C;c.1933C>T;c.1946+1G>C;c.1947-1G>A;c.1947-1G>C;c.1950G>A;c.1974_1977dupGTTT;c.2160T>A;c.2172G>T;c.2173-2A>G;c.2179G>A;c.2179G>T;c.2187G>A;c.2248_2251dupATTG;c.2302delG;c.2383C>T;c.2395_2405delCATATAGCAAAinsAGCATC;c.2405_2406+1delAGGinsT;c.2498+2T>A;c.2499-1G>A;c.2555C>T;c.2645dupC;c.2694delG;c.2867G>A;c.2938C>T;c.2956C>T;c.2981C>T;c.3056G>A;c.3111+1G>A;c.3112-1G>A;c.3124delG;c.3257_3258delAC;c.3285T>G;c.3288C>A;c.3294+1G>T;c.3294+2T>G;c.3340delG;c.3379G>T;c.3466C>T;c.3473C>A;c.3502C>T;c.3537delA;c.3774delTinsATGACTGG;c.3775_3776delAAinsTTAC;c.3801+1G>T;c.3802-1G>T;c.3911A>G;c.3915_3921delCTCCCCA;c.3920delC;c.3920C>G;c.3943G>A;c.4005+1G>T;c.4006-1G>A;c.4123+1G>A;c.4132dupA;c.4156C>T;c.4352delG

Wilson disease

Descripción enfermedad:
Wilson disease follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ATP7B gene located on chromosomal region 13q14.3. The age of onset is infantile. This disease is characterized by the toxic accumulation of copper, mainly in the liver and central nervous system, and symptomatic patients may present with hepatic, neurologic or psychiatric forms. The birth incidence is 1:30,000-1:100,000 in France and The prevalence is 1:10,000-1:30,000.

c.4195delC;c.4125-2A>G;c.4114C>T;c.4092_4093delGT;c.4088C>T;c.4058G>A;c.4051C>T;c.4039G>A;c.4022-2A>C;c.4021G>A;c.4006delA;c.3990_3993delTTAT;c.3992A>C;c.3955C>T;c.3948delG;c.3942_3943delCA;c.3904-2A>G;c.3895C>T;c.3886G>A;c.3818C>A;c.3818C>T;c.3809A>G;c.3800delA;c.3800A>C;c.3796G>A;c.3700-1G>A;c.3694A>C;c.3688A>G;c.3664delG;c.3662G>A;c.3659C>T;c.3649_3654delGTTCTG;c.3646G>A;c.3598C>T;c.3556+1G>A;c.3556+1G>T;c.3552dupT;c.3529C>T;c.3517G>A;c.3451C>T;c.3449delA;c.3443T>C;c.3436G>A;c.3402delC;c.3359T>A;c.3350_3353delAGCG;c.3317T>A;c.3305T>C;c.3301G>A;c.3295G>A;c.3284A>C;c.3263T>A;c.3244-2A>G;c.3243+1G>A;c.3236G>T;c.3207C>A;c.3191A>C;c.3182G>A;c.3157dupC;c.3147delC;c.3121C>T;c.3107dupT;c.3104G>T;c.3083delA;c.3053C>T;c.3011A>C;c.3008C>T;c.3007G>A;c.2998G>A;c.2975C>T;c.2972C>T;c.2963G>A;c.2962G>C;c.2953T>C;c.2930C>T;c.2906G>A;c.2905C>T;c.2901delC;c.2865+1G>A;c.2826_2832delCGGTTTT;c.2828G>A;c.2817G>T;c.2810delT;c.2807T>A;c.2804C>T;c.2795C>A;c.2755C>G;c.2755C>T;c.2743C>T;c.2731-2A>G;c.2730+1G>A;c.2621C>T;c.2605G>A;c.2576-2A>G;c.2575+1G>A;c.2575+1G>C;c.2570T>C;c.2532delA;c.2519C>T;c.2513delA;c.2447+2T>G;c.2438_2440delTAAinsAT;c.2428G>T;c.2383C>T;c.2356-1G>A;c.2356-1G>C;c.2356-2A>G;c.2336G>A;c.2335T>G;c.2333G>A;c.2333G>T;c.2332C>G;c.2332C>T;c.2304delC;c.2304dupC;c.2305A>G;c.2303C>T;c.2297C>G;c.2294A>G;c.2293G>A;c.2233_2234delCT;c.2217dupT;c.2165dupT;c.2157C>A;c.2149C>T;c.2145C>A;c.2131G>A;c.2128G>A;c.2123T>C;c.2122-1G>A;c.2122-8T>G;c.2097_2100delCTTT;c.2072G>T;c.2071G>A;c.2038C>T;c.2035delC;c.2009_2015delATATGCT;c.2000T>A;c.1946+6T>C;c.1934T>G;c.1924G>C;c.1877G>C;c.1847G>A;c.1846C>T;c.1820dupA;c.1782delT;c.1772G>A;c.1745_1746delTA;c.1739delA;c.1716delG;c.1708-1G>A;c.1708-1G>C;c.1708-2A>G;c.1708-5T>G;c.1639C>T;c.1605_1609dupGGTCA;c.1568T>A;c.1544-2A>C;c.1543+1G>T;c.1512dupT;c.1470C>A;c.1392dupG;c.1374_1377delAGTG;c.1372G>T;c.1340_1343delAAAC;c.1337_1338insTT;c.1285+2T>A;c.1145_1151delCCCAACT;c.1063C>T;c.994G>T;c.915T>A;c.865C>T;c.845delT;c.841C>T;c.813C>A;c.778dupC;c.738dupT;c.650T>G;c.562C>T;c.524_525delAA;c.525dupA;c.388_389dupGC;c.383delG;c.331C>T;c.314C>A;c.254G>T;c.174dupC;c.122A>G;c.111dupT;c.103A>T;c.52-1G>T;c.51+4A>T;c.19_20delCA

Cholestasis, progressive familial intrahepatic, type 1; Cholestasis, benign recurrent intrahepatic, type 1

Descripción enfermedad:
Progressive familial intrahepatic, type 1 (PFIC1) is a heterogeneous group of autosomal recessive liver disorders characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood (Alonso et al., 1994; Whitington et al., 1994; Klomp et al., 2004). Mutations in the ATP8B1 gene can cause benign recurrent intrahepatic cholestasis type 1 (BRIC1). BRIC1 is characterized by intermittent episodes of cholestasis without extrahepatic bile duct obstruction. There is initial elevation of serum bile acids, followed by cholestatic jaundice which generally spontaneously resolves after periods of weeks to months (Summerskill and Walshe, 1959; Schapiro and Isselbacher, 1963; Brenard et al., 1989). Tygstrup et al. (1999) stated that referring to this disorder as 'benign' is a misnomer, because the disease has an impact on the quality of life in some patients. They preferred the term 'recurrent familial intrahepatic cholestasis.' Mutation in the ATP8B1 gene can also cause ).

c.3410C>G;c.2854C>T;c.2674G>A;c.2599C>T;c.2286-2A>G;c.2097+2T>C;c.1993G>T;c.1982T>C;c.1804C>T;c.1660G>A;c.1367C>T;c.923G>T;c.863T>C;c.625C>A

Congenital disorder of glycosylation, type 2D

Descripción enfermedad:
Congenital disorder of glycosylation type 2D follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the B4GALT1 gene located on chromosomal region 9p13. The age of onset is neonatal/infantile. This disease is characterized by macrocephaly, hydrocephaly, hypotonia, myopathy and coagulation anomalies. The prevalence is <1:1,000,000.

c.1031dupC

Bardet-Biedl syndrome, type 1

Descripción enfermedad:
Bardet-Biedl syndrome 1 is an autosomal recessive and genetically heterogeneous ciliopathy characterized by retinitis pigmentosa, obesity, kidney dysfunction, polydactyly, behavioral dysfunction, and hypogonadism. Eight proteins implicated in the disorder assemble to form the BBSome, a stable complex involved in signaling receptor trafficking to and from cilia (summary by Scheidecker et al., 2014).

c.17dupC;c.47+2T>C;c.48-3C>G;c.48-2A>C;c.48-1G>T;c.124+1G>A;c.124+1G>C;c.159+2T>A;c.182delC;c.223_224delCT;c.416G>A;c.432+1G>A;c.433-2A>G;c.436C>T;c.479+2T>G;c.480-1G>C;c.518+1G>A;c.519-2A>G;c.724-1G>C;c.786delG;c.831-2A>G;c.851delA;c.855C>A;c.871C>T;c.887delT;c.951+1G>A;c.952-1G>A;c.952-1G>C;c.952G>A;c.981delC;c.1012C>T;c.1072delT;c.1131_1135delCTTTG;c.1169T>G;c.1232_1235delGAGG;c.1240G>T;c.1285C>T;c.1318C>T;c.1340-2A>G;c.1340-1G>T;c.1405C>T;c.1423delC;c.1424dupT;c.1514_1515delTG;c.1609-2A>T;c.1642delC;c.1643dupT;c.1645G>T;c.1713delA

Bardet-Biedl syndrome, type 10

Descripción enfermedad:
Bardet-Biedl syndrome 10 (BBS10) is characterized by progressive retinal dystrophy, obesity, polydactyly, cognitive impairment, and renal dysplasia (Stoetzel et al., 2006). BBS10 represents a major locus for BBS, with mutations in the BBS10 gene accounting for approximately 20% of BBS patients (Stoetzel et al., 2006; Zaghloul and Katsanis, 2009).

c.2119_2120delGT;c.1856_1865delAAAAATGCCA;c.1767C>A;c.1677delC;c.1677C>A;c.1677C>G;c.1599_1602delAACT;c.1547delC;c.1542delA;c.1510_1511delAT;c.1495G>T;c.1448_1452delCTCAA;c.1244delA;c.1241T>C;c.1202G>A;c.1184dupA;c.11840>A;c.11380>A;c.1091delA;c.1044_1045delTT;c.1024dupA;c.10240>A;c.959_962delGTTA;c.931T>G;c.909_912delTCAG;c.858_859dupTC;c.859del0insTC;c.850C>T;c.728_731delAAGA;c.687delT;c.6460>G;c.590A>G;c.574C>T;c.539G>A;c.531C>A;c.378G>A;c.3650>A;c.361A>T;c.273C>G;c.271dupT;c.2710>T;c.235dupA;c.215del0insGT;c.198-1G>C;c.197+1G>T;c.164T>C;c.145C>T;c.101G>C;c.83_84delGCinsAG;c.39_46delGGCGTTGC;c.32T>G

Bardet-Biedl syndrome, type 2

Descripción enfermedad:
Bardet-Biedl syndrome 2 (BBS2) is an autosomal recessive ciliopathy characterized by retinal degeneration, polydactyly, renal disease, hypogonadism, obesity, dysmorphic features, and variable degrees of cognitive impairment (Innes et al., 2010). Mutation in the BBS2 gene is the third most frequent cause of BBS, accounting for approximately 8% of cases (Zaghloul and Katsanis, 2009).

c.2107C>T;c.2060-1G>T;c.2038C>T;c.1969G>T;c.1946_1952delACCTTAA;c.1911-1G>A;c.1909_1910delAT;c.1895G>C;c.1864C>T;c.1814C>G;c.1797+1G>A;c.1780C>T;c.1770delT;c.1705C>T;c.1438C>T;c.1237C>T;c.1099dupC;c.1081-1G>T;c.1015C>T;c.941-1G>T;c.941-2A>C;c.940delA;c.823C>T;c.814C>T;c.806T>G;c.717+2T>G;c.717+1G>A;c.700C>T;c.646C>T;c.627_628delTT;c.565C>T;c.563delT;c.535-2A>G;c.534+1G>T;c.508G>A;c.472delG;c.472-2A>G;c.471+1G>A;c.416G>T;c.311A>C;c.263delG;c.224T>G;c.175C>T;c.118-1G>C;c.98C>A;c.72C>G

Maple syrup urine disease, type 1A

Descripción enfermedad:
Maple syrup urine disease, type 1A follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the BCKDHA gene located on chromosomal region 19q13.1-13.2. The age of onset is neonatal/infantile. This disease is characterized by poor feeding, lethargy, vomiting, a maple syrup odor in the cerumen and urine, encephalopathy and central respiratory failure if untreated. The prevalence is 1:1,000,000-9:1,000,000.

c.14delT;c.117delC;c.117dupC;c.127C>T;c.137C>A;c.143delT;c.288+1G>A;c.399delCinsAA;c.470A>C;c.476G>A;c.511delC;c.632C>T;c.647-1G>C;c.661_664delTACG;c.659C>T;c.718delG;c.741dupT;c.745G>A;c.797delA;c.844G>C;c.853G>C;c.853+1G>T;c.854-2A>G;c.861_868delAGGCCCCG;c.859C>T;c.868G>A;c.905A>C;c.909_910delGT;c.917delT;c.929C>G;c.940C>T;c.964C>T;c.979G>A;c.1008_1015delCAGCACCA;c.1036C>T;c.1037G>A;c.1119G>A;c.1168-2A>G;c.1198A>T;c.1226T>G;c.1234G>A;c.1310_1311delAC;c.1312T>A

Maple syrup urine disease, type 1B

Descripción enfermedad:
Maple syrup urine disease, type 1B follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the BCKDHB gene located on chromosomal region 6q14.1. The age of onset is neonatal/infantile. This disease is characterized by poor feeding, lethargy, vomiting, a maple syrup odor in the cerumen and urine, encephalopathy and central respiratory failure if untreated. The prevalence is 1:10,000-5:10,000.

c.3G>A;c.93_103delGGCGCGGGGCT;c.93_103dupGGCGCGGGGCT;c.196+1G>C;c.196+1G>T;c.197-2A>G;c.275-2A>G;c.281_291delTTGGTGAAGAT;c.302G>A;c.342T>G;c.343+2T>G;c.344-1G>A;c.348delA;c.356T>G;c.368delC;c.401T>A;c.403G>A;c.410C>T;c.479T>G;c.487G>T;c.488A>T;c.508C>A;c.508C>G;c.508C>T;c.509G>A;c.526A>T;c.547C>T;c.548G>C;c.554C>T;c.564T>A;c.592_593delCA;c.595_596delAG;c.616C>T;c.633+1G>A;c.633+1G>C;c.633+1G>T;c.730delT;c.742+1G>A;c.748G>T;c.752T>C;c.776delC;c.799C>T;c.811_824delGATGTTACTCTAGT;c.832G>A;c.840+1G>A;c.840+1G>T;c.840+2T>G;c.841-1G>C;c.853delC;c.853C>T;c.885delT;c.902T>G;c.952-2A>G;c.952-1G>A;c.964A>G;c.970C>T;c.1006G>A;c.1016C>T;c.1022T>A;c.1046G>A;c.1065delT;c.1114G>T;c.1149T>A

BCS1L-related disorders, including Leigh syndrome

Descripción enfermedad:
Leigh syndrome caused by mutations in the BCS1L gene -located on chromosomal region 2q35- follows an autosomal recessive pattern of inheritance. Leigh syndrome is a clinically and genetically heterogeneous disorder resulting from defective mitochondrial energy generation; It presents extensive genetic heterogeneity (more than 75 different genes) with mutations identified in both nuclear- and mitochondrial-encoded genes involved in energy metabolism, including mitochondrial respiratory chain complexes I, II, III, IV, and V. It most commonly presents as a progressive and severe neurodegenerative disorder with onset within the first months or years of life, and may result in early death. Affected individuals usually show global developmental delay or developmental regression, hypotonia, ataxia, dystonia, and ophthalmologic abnormalities, such as nystagmus or optic atrophy. The BCS1L protein is critical for the formation of mitochondrial complex III. This syndrome affects at least 1 in 40,000 newborns.

c.103G>C;c.133C>T;c.148A>G;c.166C>T;c.232A>G;c.245C>A;c.296C>T;c.320+1G>T;c.349C>T;c.385G>A;c.418delC;c.431G>A;c.460+1G>A;c.460+2T>C;c.464G>C;c.534delC;c.547C>T;c.548G>A;c.550C>T;c.556C>T;c.598C>T;c.607dupA;c.625_626delAT;c.655+1G>A;c.696delT;c.772delG;c.821delC;c.830G>A;c.871C>T;c.889+1G>A;c.889+1G>T;c.901T>A;c.973dupC;c.980T>C;c.1007+2_1007+5delTAGG;c.1057G>A

Bloom syndrome

Descripción enfermedad:
Bloom syndrome is an autosomal recessive disorder characterized by proportionate pre- and postnatal growth deficiency; sun-sensitive, telangiectatic, hypo- and hyperpigmented skin; predisposition to malignancy; and chromosomal instability.

c.2T>C;c.98+1G>A;c.98+1G>T;c.99-1G>C;c.205G>A;c.205G>T;c.213_214delTT;c.275delA;c.298_299delCA;c.311C>A;c.320dupT;c.443dupT;c.479_480delTT;c.557_559delCAA;c.581_582delTT;c.582delT;c.608_609delCA;c.662_665delCTGA;c.772_773delCT;c.835G>T;c.959+1_959+9delGTAAACTAG;c.991_995delAAAGA;c.1003_1006dupCTTA;c.1083_1084delTG;c.1087+1G>A;c.1088-2A>G;c.1088-1G>A;c.1129delG;c.1220+1G>A;c.1221-2A>C;c.1284G>A;c.1295dupC;c.1301C>G;c.1358T>G;c.1385delC;c.1429_1432delACAG;c.1462G>T;c.1479_1480delTA;c.1500delT;c.1544delA;c.1544dupA;c.1628T>A;c.1642C>T;c.1722_1725delAGCAinsGGC;c.1740delC;c.1752delT;c.1764_1777delGGAAGGTCGGCCAA;c.1795delA;c.1817_1820delACTG;c.1883-2A>G;c.1933C>T;c.1968dupG;c.1985_1986delAA;c.2074+1G>T;c.2098C>T;c.2193+1_2193+9delGTAAGTTAT;c.2193+2T>G;c.2206dupT;c.2207_2212delATCTGAinsTAGATTC;c.2250_2251insAAAT;c.2258T>A;c.2291_2292delAT;c.2308-2A>G;c.2343_2344dupGA;c.2406+2T>G;c.2407-1G>A;c.2407dupT;c.2488dupA;c.2506_2507delAG;c.2555+1G>T;c.2580_2581delTA;c.2643G>A;c.2662+2T>C;c.2663-2A>G;c.2695C>T;c.2720_2726delCGTTACA;c.2821C>T;c.2824-2A>T;c.2824-1G>C;c.2855G>T;c.2875C>T;c.2887C>T;c.2923delC;c.3014_3015insTATCA;c.3016_3017delAT;c.3022delG;c.3028delG;c.3107G>T;c.3164G>C;c.3191A>T;c.3197G>A;c.3210+2delT;c.3222_3223delAA;c.3223dupA;c.3255_3256insT;c.3261delT;c.3278C>G;c.3305_3306delAT;c.3400G>T;c.3415C>T;c.3439A>T;c.3475_3476delTT;c.3499delG;c.3558+1G>A;c.3558+1G>T;c.3559-1G>A;c.3566_3567delTT;c.3587delG;c.3638delA;c.3667dupA;c.3681delA;c.3692_3693delAA;c.3727dupA;c.3847C>T;c.3855C>A;c.3874+2T>C;c.3901delC;c.3917delG;c.3937G>T;c.3956delT;c.4000_4004delAGGAA

Bartter syndrome, type 4A

Descripción enfermedad:
Bartter syndrome, type 4A with deafness follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the BSND gene located on chromosomal region 1p32.3. The age of onset is neonatal/infantile. This disease is characterized by maternal polyhydramnios, premature delivery, polyuria, sensorineural deafness and is associated with hypokalemic alkalosis, increased levels of plasma renin and aldosterone, low blood pressure, and vascular resistance to angiotensin II.

c.1A>T;c.3G>A;c.10G>T;c.22C>T;c.23G>T;c.35T>C;c.139G>A

Biotinidase deficiency

Descripción enfermedad:
Biotinidase deficiency an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the BTD gene located on chromosomal region 3p25. The age of onset is neonatal/infantile. This disease is characterized by seizures, breathing difficulties, hypotonia, skin rash, alopecia, hearing loss and delayed development.

c.44+1G>A;c.44+1G>C;c.44+1G>T;c.104_110delGCGGCTGinsTCC;c.113dupA;c.124_125delCT;c.142G>T;c.166G>T;c.177T>G;c.190G>A;c.190G>T;c.196G>A;c.198G>C;c.208_211dupATCC;c.200A>G;c.241C>T;c.251C>A;c.263T>G;c.268C>T;c.272delA;c.284A>G;c.289C>T;c.304G>A;c.316-1G>T;c.316G>T;c.322C>T;c.329_330dupTA;c.332dupT;c.332T>G;c.340G>A;c.340G>C;c.347G>T;c.378_381dupCATT;c.388T>G;c.399delC;c.412delC;c.426G>A;c.430C>A;c.449G>A;c.451T>C;c.460A>C;c.461C>G;c.465G>A;c.472C>T;c.475C>T;c.476G>A;c.496_497delAG;c.517G>A;c.534G>T;c.550delA;c.563G>A;c.565C>T;c.589A>G;c.590A>G;c.593delC;c.593C>G;c.600delC;c.601G>A;c.632G>A;c.635A>G;c.637delC;c.637C>T;c.643delC;c.649C>T;c.652T>A;c.658G>C;c.660G>C;c.670G>A;c.670G>C;c.689A>G;c.699delC;c.707C>T;c.715G>A;c.740G>A;c.761A>G;c.764C>T;c.789C>G;c.800A>T;c.838C>G;c.842T>A;c.842T>G;c.871G>C;c.893T>G;c.901G>C;c.902C>T;c.904A>C;c.935G>A;c.938G>A;c.939delT;c.939T>G;c.1007T>A;c.1055delC;c.1058delC;c.1102_1103dupTC;c.1132C>T;c.1163G>A;c.1164G>A;c.1197_1198delGA;c.1213T>G;c.1233_1247delGGGAAAGGAAGGCTAinsTTCCAATGGCC;c.1245delC;c.1247_1258delATCTCCACGTCT;c.1270dupC;c.1281T>G;c.1290C>A;c.1320T>A;c.1330delG;c.1336G>C;c.1345C>T;c.1358_1359delGC;c.1358G>A;c.1367A>G;c.1374A>C;c.1378dupT;c.1390delA;c.1400dupG;c.1461C>G;c.1464delG;c.1465delT;c.1495C>T;c.1499dupT;c.1514_1518delGGATG;c.1563T>G;c.1601C>T;c.1618C>T;c.1622dupT

Agammaglobulinemia X-linked, type 1

Descripción enfermedad:
Agammaglobulinemia X-linked (XLA), type 1 follows an X-linked pattern of inheritance and is caused by pathogenic variants in the BTK gene located on chromosomal region Xq21.33-q22. The age of onset is neonatal. Individuals with XLA are more susceptible to infections because their body makes very few antibodies. In children with XLA, infections generally take longer to get better and then they come back again, even with antibiotic medications. The most common bacterial infections that occur in people with XLA are lung infections (pneumonia and bronchitis), ear infections (otitis), pink eye (conjunctivitis), and sinus infections (sinusitis). Infections that cause chronic diarrhea are also common. Recurrent infections can lead to organ damage. The X-linked form accounts for approximately 85 to 90% of cases of agammaglobulinemia. The prevalence is 3:1,000,000-6:1,000,000 men.

c.2008G>T;c.1991T>A;c.1990A>C;c.1940G>A;c.1922C>A;c.1882G>A;c.1875C>A;c.1868A>G;c.1862T>C;c.1859T>C;c.1843T>C;c.1790G>A;c.1790G>T;c.1787G>C;c.1786C>T;c.1775_1782delAATTTCCA;c.1734-2A>G;c.1733+1G>T;c.1727T>C;c.1683_1686delTTTG;c.1676G>A;c.1675C>T;c.1669-2A>T;c.1661G>A;c.1660C>G;c.1660C>T;c.1628T>C;c.1618T>C;c.1613A>T;c.1608C>A;c.1591C>T;c.1557C>A;c.1544G>C;c.1543T>A;c.1390A>G;c.1377C>A;c.1325T>C;c.1287G>A;c.1227T>G;c.1205G>A;c.1184A>G;c.1166T>A;c.1103A>C;c.1021A>G;c.997-2A>G;c.996+1G>A;c.965G>A;c.964C>T;c.942-1G>A;c.941+1G>A;c.879-2A>G;c.865C>T;c.857G>A;c.828dupT;c.820G>T;c.771T>A;c.755delA;c.744_745delTG;c.690+2T>A;c.690_690+1insCTACATAG;c.659dupA;c.574_577delACAG;c.571C>T;c.537C>A;c.491delA;c.473G>A;c.472T>C;c.440T>A;c.412-1G>C;c.412-2A>G;c.409C>T;c.380C>A;c.330_333delAAGA;c.317dupA;c.266C>A;c.263delG;c.221A>G;c.199A>C;c.185G>A;c.148C>T;c.145C>T;c.143C>A;c.139C>T;c.2T>C

Osteopetrosis with renal tubular acidosis (osteopetrosis, autosomal recessive, type 3)

Descripción enfermedad:
Osteopetrosis with renal tubular acidosis, also known as osteopetrosis, autosomal recessive, type 3, follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the CA2 gene located on chromosomal region 8q22. The age of onset is neonatal/infantile. This disease is characterized by osteopetrosis, renal tubular acidosis, and neurological disorders related to cerebral calcifications. The prevalence is <1:1.000.000.

c.120T>G;c.232+1G>A;c.319C>T;c.663+2T>C

Limb-girdle muscular dystrophy, type 1 (LGMD R1)

Descripción enfermedad:
Limb-girdle muscular dystrophy type 1 (LGMDR1; formerly LGMD2A) follows an autosomal recessive pattern of inheritance and is caused by biallelic pathogenic variants in the CAPN3 gene located on chromosomal region 15q15.1. The age of onset is variable. This disease is characterized by a variable age of onset of progressive, typically symmetrical and selective weakness and atrophy of proximal shoulder- and pelvic-girdle muscles (gluteus maximus, thigh adductors, and muscles of the posterior compartment of the limbs are most commonly affected) without cardiac or facial involvement. Clinical manifestations include exercise intolerance, a waddling gait, scapular winging and calf pseudo-hypertrophy.The prevalence is 1:100,000- 9:100,000. Genetic heterogeneity: Heterozygous mutation in the CAPN3 gene can cause autosomal dominant limb-girdle muscular dystrophy-4 (LGMDD4; OMIM 618129), which has a later onset and milder features.

c.59delC;c.133G>A;c.145C>T;c.146G>A;c.223dupT;c.245C>T;c.257C>T;c.258dupT;c.310G>T;c.319G>T;c.327_328dupCC;c.328C>T;c.402delC;c.439C>T;c.483delG;c.499-1G>A;c.503G>A;c.509A>G;c.518G>A;c.533T>C;c.550delA;c.580delT;c.598_612delTTCTGGAGTGCTCTG;c.639dupT;c.640G>A;c.649G>A;c.664G>A;c.701G>A;c.717delT;c.741_751delCATGTACAAGA;c.742_743delAT;c.759_761delGAA;c.801+1G>A;c.802-9G>A;c.853dupG;c.855_864dupGTTGATTGCA;c.865C>T;c.883_886delGATAinsCTT;c.946-1G>A;c.956C>T;c.985G>A;c.1027G>T;c.1030-1G>A;c.1043delG;c.1063C>T;c.1069C>T;c.1079G>A;c.1080G>C;c.1115+1G>A;c.1115+2T>A;c.1115+2T>C;c.1118G>A;c.1127G>A;c.-3311A>G;c.1234G>T;c.1250C>T;c.1256A>G;c.1257T>G;c.1276_1277delCT;c.1292dupT;c.1298_1299delTG;c.1303G>A;c.1309C>T;c.1318C>T;c.1322delG;c.1319G>A;c.1333G>A;c.1342C>G;c.1342C>T;c.1343G>A;c.1355-1G>C;c.1373delC;c.1381C>T;c.1435A>G;c.1465C>T;c.1466G>A;c.1468C>T;c.1469G>A;c.1477C>T;c.1517T>C;c.1524+1G>A;c.1524+1G>T;c.1524+2T>C;c.1599_1602delGAGC;c.1611C>A;c.1621C>T;c.1622G>A;c.1636C>T;c.1642delC;c.1662C>G;c.1699G>T;c.1711delC;c.1714C>T;c.1715G>A;c.1722delC;c.1743_1744delTG;c.1771delG;c.1795dupA;c.1801-1G>A;c.1817C>T;c.1838delA;c.1855C>T;c.1858G>T;c.1863dupA;c.1882delA;c.1914+2T>C;c.1939G>T;c.1944_1945delTG;c.1948G>T;c.1957C>T;c.1981delA;c.1992+1G>T;c.1992+2T>A;c.1993-1G>A;c.1999dupG;c.2007T>A;c.2036_2037delCA;c.2050+1delG;c.2050+1G>A;c.2051-1G>C;c.2051-1G>T;c.2069_2070delAC;c.2092C>T;c.2105C>T;c.2115+1_2115+2dupGT;c.2115+1G>A;c.2115+2T>C;c.2120A>G;c.2134C>T;c.2179delT;c.2184+2T>C;c.2185-2A>G;c.2207_2208delCA;c.2212C>T;c.2242C>T;c.2243G>A;c.2251_2254dupGTCA;c.2263+1G>A;c.2279dupA;c.2288A>G;c.2290delG;c.2305C>T;c.2306G>A;c.2314_2317delGACA;c.2338G>C;c.2361_2362insTC;c.2362_2363delAGinsTCATCT;c.2380+1G>T;c.2381-2A>G;c.2381-1G>A;c.2393C>A;c.2440-2A>G;c.2440-1G>A

Homocystinuria due to cystathionine beta-synthase

Descripción enfermedad:
Homocystinuria due to cystathionine beta-synthase follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the CBS gene located on chromosomal region 21q22.3. The age of onset is infantile. This disease is characterized by the multiple involvement of the eye, skeleton, central nervous system and vascular system. The prevalence is 1:200,000-1:335,000.

c.1566delG;c.1552+1G>A;c.1545delG;c.1468-1G>A;c.1359-1G>C;c.1358+2T>C;c.1358+1G>A;c.1330G>A;c.1321A>T;c.1280C>T;c.1224-2A>C;c.1219_1223+8delCCCTGGTAAGACC;c.1223G>A;c.1221delC;c.1218delG;c.1150A>G;c.1136G>A;c.1111G>A;c.1109G>A;c.1087delG;c.1058C>T;c.1039G>A;c.1009_1012delATGC;c.1007G>A;c.1006C>T;c.992C>A;c.969G>A;c.959T>C;c.954+2T>G;c.954+1G>A;c.919G>A;c.904G>A;c.903C>G;c.833T>C;c.829-1G>C;c.828+1G>A;c.816T>A;c.797G>A;c.785C>T;c.770C>T;c.738delG;c.737-1G>C;c.736+2T>G;c.707_708delCCinsGGTG;c.700G>A;c.689delT;c.676G>A;c.667-14_667-7delCTCTTTCT;c.572C>T;c.532-2A>G;c.526G>T;c.502G>A;c.494G>A;c.467delT;c.451+1G>T;c.442G>A;c.434C>T;c.430G>A;c.415G>A;c.402delG;c.393G>C;c.374G>A;c.373C>T;c.362G>A;c.346G>A;c.341C>T;c.325T>C;c.316+1G>A;c.306G>C;c.302T>C;c.253G>A;c.233C>G;c.209+2T>C;c.209+1G>C;c.153_165delGTGCACCTGGCAG;c.162G>A;c.146C>T;c.28delG;c.19dupC

Hyper-IgM syndrome, type 1 (immunodeficiency, X-linked, with hyper-IgM, type 1)

Descripción enfermedad:
Hyper-IgM syndrome, type 1, also known as X-linked immunodeficiency with hyper-IgM, type 1 (HIGM1) follows an X-linked pattern of inheritance and is caused by pathogenic variants in the CD40LG gene located on chromosomal region Xq26. The age of onset is neonatal/infantile. This disease is characterized by lower-respiratory tract bacterial infections, opportunistic infections, recurrent or protracted diarrhea associated with failure to thrive, neutropenia, thrombocytopenia and anemia. The prevalence is 2:1,000,000 male newborns.

c.31C>T;c.107T>G;c.189delT;c.216C>A;c.346+1delG;c.347-2A>G;c.368C>A;c.418T>G;c.419G>A;c.431G>A;c.440C>A;c.464T>C;c.506A>G;c.559delG;c.658C>T;c.680G>T;c.703G>C;c.719_720delAT;c.761C>T;c.767T>C

Deafness, autosomal recessive, type 12; Usher syndrome, type 1D

Descripción enfermedad:
Non-syndromic autosomal recessive deafness, type 12 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the CDH23 gene located on chromosomal region 10p22.1. The age of onset is neonatal/infantile. This disease is characterized by congenital, non-progressive, mild-to-profound sensorineural hearing impairment. Mutation in the CDH23 gene can also cause the more severe Usher syndrome 1D. Usher syndrome type 1 is an autosomal recessive condition characterized by profound congenital hearing impairment with unintelligible speech, early retinitis pigmentosa (usually evident within the first decade), and constant vestibular dysfunction.

c.46delG;c.146-2A>G;c.193delC;c.288+1G>A;c.288+1G>C;c.380A>G;c.478G>A;c.945+1G>A;c.945+1G>T;c.1036C>T;c.1037C>T;c.1428dupG;c.1675C>T;c.1858+2T>G;c.1949dupC;c.1987-1G>A;c.2012delT;c.2289+1G>A;c.3141C>A;c.3181G>A;c.3221-2A>G;c.3241C>T;c.3481C>T;c.3516_3519delATCC;c.3579+2T>C;c.3628C>T;c.3706C>T;c.3880C>T;c.4021G>A;c.4309C>T;c.4504C>T;c.5237G>A;c.5272C>T;c.5663T>C;c.5712+1G>A;c.5923+1G>A;c.6049+1G>A;c.6050-9G>A;c.6133G>A;c.6253+1G>A;c.6393delC;c.6402_6405delAGAG;c.6412delG;c.6442G>A;c.6604G>A;c.6614C>T;c.6667delC;c.6712+1G>A;c.6968delC;c.7054+1G>A;c.7225-1G>A;c.7362G>A;c.7483-1G>C;c.7660+1G>T;c.7776G>A;c.7873-2A>T;c.7908C>G;c.7921G>C;c.7979_7986delACTGGGAG;c.8064+1G>T;c.8222C>A;c.8770_8771insTGGCTGTA;c.8781C>A;c.9129delG;c.9556C>T;c.9629_9632delTCAA

Meckel syndrome, type 4; Joubert syndrome, type 5; Leber congenital amaurosis, type 10

Descripción enfermedad:
Meckel syndrome type 4 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the CEP290 gene located on chromosomal region 12q21.32. The age of onset is neonatal. This disease is characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically occipital encephalocele), hepatic ductal dysplasia and cysts, and postaxial polydactyly. The prevalence is <1/1,000,000. Other ciliopathies are associated with mutation in CEP290 gene as Joubert syndrome, type 5 and Leber congenital amaurosis, type 10. Joubert syndrome (JBTS) is an autosomal recessive disorder presenting with psychomotor delay, hypotonia, ataxia, oculomotor apraxia, and neonatal breathing abnormalities (Valente et al., 2006). Leber congenital amaurosis is a severe retinal dystrophy, causing blindness or severe visual impairment at birth or during the first months of life (den Hollander et al., 2006).

c.7341delA;c.7341dupA;c.7324G>T;c.7062_7063delGA;c.6939C>A;c.6869dupA;c.6798G>A;c.6645+1G>A;c.6624delG;c.6604delA;c.6516delA;c.6448_6455delCAGTTGAA;c.6364A>T;c.6358-1G>A;c.6277delG;c.6135+2T>A;c.6072C>A;c.5932C>T;c.5850delT;c.5803G>T;c.5707A>T;c.5704G>T;c.5668G>T;c.5649dupA;c.5611_5614delCAAA;c.5493delA;c.5434_5435delGA;c.5344C>T;c.5212G>T;c.5182G>T;c.5012+2T>C;c.4966_4967delGA;c.4966G>T;c.4962_4963delAA;c.4960C>T;c.4916C>A;c.4882C>T;c.4813-2A>G;c.4811G>A;c.4801C>T;c.4723A>T;c.4705-1G>T;c.4656delA;c.4621delA;c.4522C>T;c.4452_4455delAGAA;c.4438-3delC;c.4437+1G>A;c.4393C>T;c.4384delG;c.4276_4277delAA;c.4243G>T;c.3943G>T;c.3904C>T;c.3784_3785insTT;c.3777_3778delAG;c.3461+1G>A;c.3446_3447delAA;c.3190delA;c.3185delT;c.3181_3182delAT;c.3176delT;c.3175delA;c.3175dupA;c.3104-2A>G;c.3097A>T;c.3012delA;c.2991+1655A>G;c.2969delC;c.2941C>T;c.2911G>T;c.2722C>T;c.2668C>T;c.2251C>T;c.2248_2249delTT;c.2249T>G;c.2112delA;c.2052+1_2052+2delGT;c.1984C>T;c.1936C>T;c.1915G>T;c.1860_1863delAAGA;c.1860_1861delAA;c.1781T>A;c.1711+1G>A;c.1709C>G;c.1681C>T;c.1665_1666delAA;c.1666delA;c.1623+1G>A;c.1523-1G>T;c.1512_1515delAGAG;c.1501G>T;c.1474A>T;c.1451delA;c.1429C>T;c.1419_1423delAATAA;c.1219_1220delAT;c.1190-2A>G;c.1078C>T;c.1066-1G>A;c.828delA;c.673_674delTT;c.654T>G;c.613C>T;c.508A>T;c.451C>T;c.437delA;c.384_387delTAGA;c.381_382delAGinsT;c.289G>T;c.268A>T;c.181-2A>G;c.180+2T>A;c.180+1G>A;c.164_167delCTCA;c.103-1G>T;c.21G>T

Retinitis pigmentosa, type 26

Descripción enfermedad:
Retinitis pigmentosa, type 26 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the CERKL gene located on chromosomal region 2q31.3. The age of onset is variable. This disease is characterized by night blindness (nyctalopia), peripheral visual field impairment and over time loss of central vision. The prevalence is 1:10,000-5:10,000.

c.1425T>A;c.1381C>T;c.1090C>T;c.1045_1046delAT;c.858delT;c.847C>T;c.598A>T;c.481+2T>G;c.420delT;c.312delA;c.239-1G>A;c.239-2A>G

Cystic fibrosis

Descripción enfermedad:
Cystic fibrosis follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the CFTR gene located on chromosomal region 7q31.2. The age of onset of severe form is neonatal or infantile but there are also variants associated with moderate clinical or late onset. This disease is characterized by the production of sweat with a high salt content, mucus secretions with an abnormal viscosity, chronic bronchitis, pancreatic insufficiency, adolescent diabetes and, more rarely, stercoral obstruction and cirrhosis. Male sterility is a constant feature. Late-onset forms, which are usually only mild or monosymptomatic. The prevalence is 1:10,000-9:10,000.

c.1A>G;c.4C>T;c.11C>A;c.50delT;c.44T>C;c.53+1G>T;c.57G>A;c.79G>T;c.88C>T;c.115C>T;c.137C>A;c.164+1G>A;c.164+1G>T;c.164+2T>C;c.164+4dupT;c.165-3C>T;c.165-1G>A;c.166G>A;c.169T>G;c.170G>A;c.171G>A;c.174_177delTAGA;c.175dupA;c.178G>A;c.178G>T;c.200C>T;c.223C>T;c.233dupT;c.254G>A;c.262_263delTT;c.263T>A;c.263T>G;c.271G>A;c.273+1G>A;c.273+3A>C;c.274-2A>G;c.274-1G>A;c.274G>A;c.274G>T;c.292C>T;c.305T>G;c.310delA;c.313delA;c.325_327delTATinsG;c.328G>C;c.328G>T;c.349C>T;c.350G>A;c.350G>T;c.366T>A;c.409delC;c.413_415dupTAC;c.416A>G;c.442delA;c.445G>A;c.445G>T;c.446G>T;c.489+1G>T;c.531delT;c.532G>A;c.543_546delTAGT;c.571T>G;c.577G>T;c.579+1G>T;c.579+3A>G;c.579+5G>A;c.580-1G>T;c.595C>T;c.613C>T;c.617T>G;c.647G>A;c.658C>T;c.680T>G;c.695T>A;c.708delT;c.717delG;c.803delA;c.825C>G;c.828C>A;c.850dupA;c.861_865delCTTAA;c.935_937delTCT;c.933C>G;c.948delT;c.987delA;c.988G>T;c.1000C>T;c.1001G>T;c.1006_1007insG;c.1007T>A;c.1013C>T;c.1021_1022dupTC;c.1021T>C;c.1029delC;c.1037T>C;c.1040G>A;c.1040G>C;c.1055G>A;c.1075C>A;c.1079C>A;c.1081delT;c.1116+1G>A;c.1117-1G>A;c.1130dupA;c.1155_1156dupTA;c.1202G>A;c.1203G>A;c.1209+1G>A;c.1211delG;c.1240C>T;c.1301_1307delCACTTCT;c.1327_1330dupGATA;c.1340delA;c.1364C>A;c.1365_1366delGG;c.1393-2A>G;c.1393-1G>A;c.1397C>A;c.1397C>G;c.1400T>C;c.1418delG;c.1420G>A;c.1438G>T;c.1466C>A;c.1475C>T;c.1477_1478delCA;c.1477C>T;c.1487G>A;c.1505T>C;c.1519_1521delATC;c.1521_1523delCTT;c.1538A>G;c.1545_1546delTA;c.1558G>T;c.1572C>A;c.1573C>T;c.1584+1G>A;c.1585-8G>A;c.1585-1G>A;c.1624G>T;c.1645A>C;c.1646G>A;c.1647T>G;c.1648G>T;c.1650delA;c.1651G>A;c.1652G>A;c.1654C>T;c.1657C>T;c.1670delC;c.1673T>C;c.1675G>A;c.1679G>A;c.1679G>C;c.1679+1G>A;c.1679+1G>C;c.1680-886A>G;c.1680-1G>A;c.1682C>A;c.1692delA;c.1703delT;c.1705T>G;c.1721C>A;c.1753G>T;c.1766+1G>A;c.1766+1G>C;c.1766+1G>T;c.1766+3A>G;c.1766+5G>T;c.1792_1798delAAAACTA;c.1826A>G;c.1882G>C;c.1923_1931delCTCAAAACTinsA;c.1973_1985delGAAATTCAATCCTinsAGAAA;c.1986_1989delAACT;c.2012delT;c.2017G>T;c.2052delA;c.2052dupA;c.2051_2052delAAinsG;c.2053dupC;c.2053C>T;c.2125C>T;c.2128A>T;c.2143C>T;c.2158C>T;c.2175dupA;c.2195T>G;c.2215delG;c.2241_2248delGATACTGC;c.2290C>T;c.2353C>T;c.2374C>T;c.2423_2424dupAT;c.2453delT;c.2463_2464delTG;c.2464G>T;c.2490+1G>A;c.2491G>T;c.2537G>A;c.2538G>A;c.2547C>A;c.2551C>T;c.2583delT;c.2589_2599delAATTTGGTGCT;c.2601dupA;c.2645G>A;c.2657+5G>A;c.2658-1G>C;c.2668C>T;c.2735C>A;c.2737_2738insG;c.2739T>A;c.2763_2764dupAG;c.2780T>C;c.2810dupT;c.2825delT;c.2834C>T;c.2869_2870insG;c.2875delG;c.2896delA;c.2908G>C;c.2930C>T;c.2936A>T;c.2988G>A;c.2988+1G>A;c.2989-2A>G;c.2989-1G>A;c.3002_3003delTG;c.3011_3019delCTATAGCAG;c.3017C>A;c.3039delC;c.3039dupC;c.3067_3072delATAGTG;c.3107C>A;c.3124C>T;c.3139_3139+1delGG;c.3140-26A>G;c.3160C>G;c.3181G>C;c.3194T>C;c.3196C>T;c.3197G>A;c.3205G>A;c.3209G>A;c.3230T>C;c.3266G>A;c.3276C>A;c.3276C>G;c.3292T>C;c.3293G>A;c.3294G>A;c.3294G>C;c.3294G>T;c.3302T>A;c.3302T>G;c.3304A>T;c.3310G>T;c.3353C>T;c.3368-2A>G;c.3435G>A;c.3454G>C;c.3468G>A;c.3468+5G>A;c.3472C>T;c.3484C>T;c.3528delC;c.3532_3535dupTCAA;c.3536_3539delCCAA;c.3587C>G;c.3605delA;c.3611G>A;c.3612G>A;c.3659delC;c.3691delT;c.3700A>G;c.3717+4A>G;c.3717+5G>A;c.3717+40A>G;c.3718-2477C>T;c.3718-3T>G;c.3718-1G>A;c.3719T>G;c.3731G>A;c.3744delA;c.3747delG;c.3752G>A;c.3761T>G;c.3763T>C;c.3764C>A;c.3773dupT;c.3846G>A;c.3848G>T;c.3873+1G>A;c.3873+2T>C;c.3883_3886delATTT;c.3883delA;c.3889dupT;c.3891dupT;c.3908delA;c.3909C>G;c.3937C>T;c.3971T>C;c.4036_4042delCTAAGCC;c.4046G>A;c.4077_4080delTGTTinsAA;c.4086dupT;c.4111G>T;c.4127_4131delTGGAT;c.4144C>T;c.4147dupA;c.4197_4198delCT;c.4231C>T;c.4234C>T;c.4242+1G>A;c.4242+1G>T;c.4251delA;c.4300_4301dupAG;c.4426C>T

Myasthenic syndrome, congenital, type 6, presynaptic

Descripción enfermedad:
Congenital myasthenic syndromes (CMS) are a group of inherited disorders affecting the neuromuscular junction (NMJ). Patients present clinically with onset of variable muscle weakness between infancy and adulthood. These disorders have been classified according to the location of the defect: presynaptic, synaptic, and postsynaptic. Myasthenic syndrome, congenital, type 6, presynaptic (CMS6) is an autosomal recessive CMS resulting from a presynaptic defect; patients have onset of symptoms in infancy or early childhood and tend to have sudden apneic episodes. Treatment with acetylcholinesterase inhibitors may be beneficial (Engel et al., 2015).

c.406G>A;c.418C>T;c.620G>A;c.1642C>T

Choroideremia

Descripción enfermedad:
Choroideremia is an X-linked disease that leads to the degeneration of the choriocapillaris, the retinal pigment epithelium, and the photoreceptor of the eye (Cremers et al., 1990). The characteristic lesion of choroideremia is chorioretinal scalloped atrophy in the midperipheral fundus, with preservation of the macula (Li et al., 2014).

c.1771-1G>A;c.1609+2T>A;c.1584_1587delTGTT;c.1497C>A;c.1484C>A;c.1471G>T;c.1437dupA;c.1342C>T;c.1334C>G;c.1218C>A;c.1213C>T;c.1144G>T;c.1138C>T;c.1019C>A;c.969T>A;c.877C>T;c.820-2A>G;c.808C>T;c.799C>T;c.757C>T;c.715C>T;c.649_652delTACT;c.525_526delAG;c.315_318delTCAG;c.280delA;c.133G>T;c.130G>T;c.116+1G>A;c.116+1G>T;c.49+1G>T

Myasthenic syndrome, congenital, type 4B, fast-channel; Myasthenic syndrome, congenital, type 4C, associated with acetylcholine receptor deficiency

Descripción enfermedad:
Congenital myasthenic syndromes (CMS) are a group of inherited disorders affecting the neuromuscular junction (NMJ). Patients present clinically with onset of variable muscle weakness between infancy and adulthood. These disorders have been classified according to the location of the defect: presynaptic, synaptic, and postsynaptic, as well as by pathologic mechanism and electrophysiologic studies (i.e., acetylcholine receptor (AChR) deficiency, slow-channel or fast-channel kinetic defects at the AChR) ( Engel et al., 2003; Engel et al., 2015). Mutations in the CHRNE gene cause fast-channel congenital myasthenic syndrome (FCCMS), a disorder of the postsynaptic neuromuscular junction (NMJ) characterized by early-onset progressive muscle weakness. The disorder results from kinetic abnormalities of the AChR channel, specifically from abnormally brief opening and activity of the channel, with a rapid decay in endplate current and a failure to reach the threshold for depolarization. Treatment with pyridostigmine or amifampridine may be helpful; quinine, quinidine, and fluoxetine should be avoided (Sine et al., 2003 and Engel et al., 2015). Mutation in the CHRNE gene can also cause congenital myasthenic syndrome, type 4C (CMS4C) associated with acetylcholine receptor (AChR) deficiency. CMS4C associated with AChR deficiency is a disorder of the postsynaptic neuromuscular junction (NMJ) clinically characterized by early-onset muscle weakness with variable severity. Electrophysiologic studies show low amplitude of the miniature endplate potential (MEPP) and current (MEPC) resulting from deficiency of AChR at the endplate. Patients with mutations in the CHRNE gene may have compensatory increased expression of the fetal subunit CHRNG (100730) and may respond to treatment with cholinergic agents, pyridostigmine, or amifampridine (Engel et al., 2015).

c.1327delG;c.1326+1G>A;c.1291G>C;c.1181_1187dupTGTTTGA;c.1161_1162insT;c.1093delG;c.1090dupC;c.1033-1G>C;c.1033-2A>T;c.1030delC;c.991C>T;c.971delT;c.918-1G>A;c.905C>G;c.865C>T;c.850A>C;c.794delC;c.794C>T;c.764C>T;c.721C>T;c.614_620delGGGCCAT;c.500G>T;c.422C>T;c.421C>A;c.344+1G>A;c.250C>T;c.223T>C;c.183_187dupCTCAC;c.130dupG

Ceroid lipofuscinosis, neuronal, type 3

Descripción enfermedad:
Neuronal ceroid lipofuscinosis, type 3 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the CLN3 gene located on chromosomal region 16p12.1. The age of onset is infantile. This disease is characterized by onset at early school age with vision loss due to retinopathy, seizures and the decline of mental and motor capacities. The annual birth incidence is 1:217,000-1:450,000 in Sweden and 1:143,000 in Germany, and the prevalence is 1.5:1,000,000-9:1,000,000.

c.1272delG;c.1247A>G;c.1198-1G>T;c.1195G>T;c.1116C>G;c.1059C>A;c.1056G>C;c.1054C>T;c.1048delC;c.1001G>A;c.1000C>T;c.988G>A;c.988G>T;c.979C>T;c.963-1G>A;c.963-1G>T;c.963-2A>C;c.962+1G>A;c.949C>T;c.944dupA;c.906+2T>A;c.883G>A;c.883G>T;c.816_817delGG;c.791-1G>A;c.784A>T;c.750delG;c.683dupT;c.677+1G>T;c.631C>T;c.622dupT;c.597C>A;c.586dupG;c.569delG;c.565G>C;c.558_559delAG;c.560G>C;c.533+1G>A;c.533+1G>C;c.509T>C;c.494G>A;c.485C>G;c.482C>G;c.472G>C;c.461-1G>A;c.461-1G>C;c.424delG;c.400T>C;c.378_379dupCC;c.379delC;c.374G>A;c.371_372insT;c.370dupT;c.302T>C;c.295-2A>C;c.281_282delCT;c.265C>T;c.240delG;c.233dupG;c.223-1G>A;c.222+2T>G;c.214C>T;c.195dupC;c.141delC;c.126-1G>A;c.105G>A;c.49G>T;c.47-1G>A;c.46+1G>A;c.46+1G>C;c.17delG;c.1A>C

Ceroid lipofuscinosis, neuronal, type 5

Descripción enfermedad:
Neuronal ceroid lipofuscinosis, type 5 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the CLN5 gene located on chromosomal region 3q21.1-q32. The age of onset is infantile. This disease is characterized by onset during infancy or early childhood with decline of mental and motor capacities, epilepsy and vision loss through retinal degeneration. The prevalence is <1:1,000,000.

c.225G>A;c.291dupC;c.335G>C;c.377G>A;c.433C>T;c.518delG;c.524T>G;c.526dupA;c.527_528insA;c.565C>T;c.575A>G;c.593T>C;c.595C>T;c.613C>T;c.620G>C;c.669dupC;c.672delG;c.671G>A;c.694C>T;c.712+1G>A;c.822G>A;c.835G>A;c.919delA;c.924_925delAT;c.1026C>A;c.1054G>T;c.1071_1072delCT;c.1072_1073delTT;c.1083delT;c.1103_1106delAACA;c.1121A>G;c.1175_1176delAT

Ceroid lipofuscinosis, neuronal, type 6

Descripción enfermedad:
Neuronal ceroid lipofuscinosis, type 6 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the CLN6 gene located on chromosomal region 15q23. The age of onset is infantile. This disease is characterized by onset during infancy or early childhood with decline of mental and motor capacities, epilepsy and vision loss through retinal degeneration. The prevalence is <1:1,000,000.

c.898T>C;c.890delC;c.665+1G>A;c.665G>A;c.663C>G;c.552dupC;c.543G>A;c.542+1G>T;c.498dupT;c.486+2T>C;c.486+1G>A;c.407G>A;c.395_396delCT;c.316dupC;c.297+1G>A;c.268_271dupAACG;c.214G>T;c.200T>C;c.198+1G>A;c.167G>A;c.150C>G;c.84-1G>A;c.83+2T>G;c.7delG

Ceroid lipofuscinosis, neuronal, type 8

Descripción enfermedad:
Neuronal ceroid lipofuscinosis, type 8 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the CLN8 gene located on chromosomal region 8p23.3. The age of onset is infantile. This disease is characterized by onset during infancy or early childhood with decline of mental and motor capacities, epilepsy, and vision loss through retinal degeneration. The prevalence is <1:1,000,000.

c.47delT;c.66delG;c.88delG;c.88G>C;c.204delC;c.226C>T;c.227A>G;c.263delA;c.283A>T;c.306G>A;c.312G>A;c.415C>T;c.470A>G;c.473A>G;c.499G>T;c.509C>T;c.543+1G>T;c.544-2A>G;c.562_563delCT;c.581A>G;c.610C>T;c.709G>A;c.763C>T;c.766C>G;c.789G>C

Usher syndrome, type 3A

Descripción enfermedad:
Usher syndrome type 3A follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the CLRN1 gene located on chromosomal region 3q25.1. The age of onset is neonatal/infantile. This disease is characterized by the association of sensorineural deafness with retinitis pigmentosa and progressive vision loss. The prevalence is 1:1.000.000- 9/1.000.000.

c.669_670insT;c.658C>T;c.630dupT;c.567T>G;c.541dupA;c.372delT;c.540C>A;c.301_305delGTCAT;c.189C>A;c.149_152delCAGGinsTGTCCAAT;c.144T>G;c.118T>G;c.92C>T

Achromatopsia, type 3

Descripción enfermedad:
Achromatopsia type 3 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the CNGB3 gene located on chromosomal region 8q21.3. The age of onset is neonatal/Infantile. This disease is characterized by reduced visual acuity, pendular nystagmus, increased sensitivity to light (photophobia), a small central scotoma, and reduced or complete loss of color discrimination. Most individuals have complete form, with total lack of function in all three types of cones. Rarely, individuals have incomplete form, with similar, but generally less severe symptoms. The prevalence is 1/30,000-1/50,000.

c.2359delA;c.2221delG;c.2103+1G>A;c.2086C>T;c.2048_2049delCA;c.2011G>T;c.1937delT;c.1929-2A>G;c.1928+2T>C;c.1908delG;c.1815delT;c.1810C>T;c.1782-2A>C;c.1781+1delG;c.1781+1G>A;c.1781+1G>C;c.1662+1G>A;c.1635T>A;c.1579-1G>A;c.1579-2A>G;c.1578+1G>A;c.1578+1G>T;c.1566_1569dupCGAC;c.1534delAinsGT;c.1516delG;c.1493delT;c.1481-2A>C;c.1480+1G>A;c.1460G>A;c.1447T>G;c.1432C>T;c.1430_1431delAGinsC;c.1426C>T;c.1366delC;c.1304C>T;c.1299_1300delGT;c.1285delT;c.1285dupT;c.1260delT;c.1255G>T;c.1243C>T;c.1208G>A;c.1194T>G;c.1179-2A>T;c.1148delC;c.1119G>A;c.1098_1101dupTAAT;c.1063C>T;c.1056-2A>G;c.1005dupT;c.1006G>T;c.904-2A>T;c.893_897delCAAAA;c.887_896delCTTCTACAAA;c.886_896delACTTCTACAAAinsT;c.886_890delACTTC;c.882C>G;c.873delGinsCAAAC;c.852+1G>C;c.819_826delCAGACTCC;c.791_794delACCT;c.756C>G;c.702_706delTTTTAinsGTTTTT;c.706delAinsTT;c.702T>A;c.682dupG;c.646C>T;c.644-1G>C;c.643+2T>C;c.607C>T;c.589_590delTT;c.567delG;c.556_559delAGGC;c.494-2A>T;c.446_447insT;c.412delA;c.393_394delGCinsTCCTGGTGA;c.391C>T;c.301C>T;c.281_284delCAAC;c.265C>T;c.257delC;c.220_221delTC;c.208C>T;c.190delG;c.163dupA;c.130-1G>T;c.129+2T>C;c.112C>T;c.95dupA;c.31dupG;c.29dupA;c.3G>A;c.2T>C

Alport syndrome, autosomal recessive, type 2

Descripción enfermedad:
Alport syndrome, autosomal recessive, type 2 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the COL4A3 and COL4A4 genes located on chromosomal region 2q36.3. The age of onset is infantile. This disease is characterized by renal, cochlear, and ocular involvement. Renal disease progresses from microscopic hematuria to proteinuria, progressive renal insufficiency, and end-stage renal disease. Progressive sensorineural hearing loss is usually present by late childhood or early adolescence. Ocular findings include anterior lenticonus, maculopathy, corneal endothelial vesicles, and recurrent corneal erosion. The prevalence is 1:50,000 newborn.

c.2T>C;c.279+1G>A;c.325-1G>A;c.345delG;c.388-1G>T;c.391G>T;c.468+1G>A;c.468+1G>T;c.547-1G>T;c.645+2T>C;c.663_664delAG;c.713dupC;c.765+2T>C;c.829-2A>C;c.898G>A;c.949_950delAG;c.1201G>A;c.1216C>T;c.1354G>A;c.1504+1G>A;c.1758+1G>A;c.1918G>A;c.1927+2T>C;c.1928-1G>A;c.2031_2038dupATCCCTGG;c.2083G>A;c.2111delC;c.2215G>A;c.2223+1G>A;c.2371C>T;c.2417dupC;c.2452G>A;c.2535delC;c.2621_2622delGAinsT;c.2747-1G>C;c.2768_2778delTAAAGGGCCAG;c.2838_2839delGA;c.2881+1G>T;c.2954G>T;c.3068_3069delCA;c.3070+2T>C;c.3109C>T;c.3148C>T;c.3210+1G>A;c.3211-1G>C;c.3244_3247delAAAG;c.3250G>T;c.3499G>A;c.3751+1G>A;c.3829G>A;c.3883-2A>G;c.4347_4353delCCGACAC;c.4420_4424delCTTTT;c.4441C>T;c.4486C>T;c.4546C>T;c.4571C>G;c.4640+1G>A;c.4756-1G>A;c.4803delT;c.4819G>T;c.4825C>T;c.4872C>G;c.4994G>A

Alport syndrome, autosomal recessive, type 2

Descripción enfermedad:
Alport syndrome, autosomal recessive, type 2 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the COL4A3 and COL4A4 genes located on chromosomal region 2q36.3. The age of onset is infantile. This disease is characterized by renal, cochlear, and ocular involvement. Renal disease progresses from microscopic hematuria to proteinuria, progressive renal insufficiency, and end-stage renal disease. Progressive sensorineural hearing loss is usually present by late childhood or early adolescence. Ocular findings include anterior lenticonus, maculopathy, corneal endothelial vesicles, and recurrent corneal erosion. The prevalence is 1:50,000 newborn.

c.4923C>A;c.4809+1G>A;c.4768C>T;c.4760delC;c.4715C>T;c.4679_4683delGCCCC;c.4623C>G;c.4599T>G;c.4429G>T;c.4394G>A;c.4333+2T>C;c.4129C>T;c.4002_4005dupACCA;c.3967C>T;c.3734G>T;c.3713C>A;c.3601G>A;c.3222dupA;c.3151-2A>G;c.2969-1G>C;c.2967_2968delAG;c.2906C>G;c.2878G>A;c.2690G>A;c.2638delG;c.2546-1G>C;c.2545+2T>G;c.2420delG;c.2320G>C;c.2312delG;c.2279dupG;c.1889delC;c.1697-1G>A;c.1696+1G>A;c.1696+1G>T;c.1623+1G>A;c.1405G>T;c.1369+1G>A;c.1118G>A;c.1100-2A>C;c.1045C>T;c.1030-1G>C;c.1030-2A>C;c.1029+2T>C;c.975+1G>A;c.975+1G>C;c.871-1G>C;c.673_680delCCAGGGCG;c.657+1G>T;c.594+1G>A;c.489+1G>A;c.372+2T>G;c.328-1G>A;c.114+1G>C;c.71+1G>A;c.71G>A

Dystrophic epidermolysis bullosa (DEB), Hallopeau-Siemens (HS) type and non-HS type; DEB pruriginosa; DEB pretibial

Descripción enfermedad:
Dystrophic epidermolysis bullosa (DEB), Hallopeau-Siemens (HS) type, follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the COL7A1 gene located on chromosomal region 3p21.1. The age of onset is neonatal/infantile. This disease is characterized by generalized cutaneous and mucosal blistering and scarring associated with severe deformities and major extracutaneous involvement. Some mutations may also cause a milder recessive form (non-HS type). Also, distint subclinical types of DEB include like Pruriginosa form (OMIM 604129), Pretibial form (OMIM 131850) and other are caused by mutations in this gene with variable modes of inheritace, including subclinical types caused by dominant mutations. In addition, less commonly, mutations in the COL7A1 gene may cause strictly dominant DEB. The overall prevalence of DEB is <1:1,000,000.

c.8524_8527+10delGAAGGTGAGGACAG;c.8479C>T;c.8440C>T;c.8393T>A;c.8371C>T;c.8329C>T;c.8245G>A;c.7957G>A;c.7930-1G>C;c.7912G>T;c.7865G>A;c.7864C>T;c.7828C>T;c.7723G>A;c.7557+1G>T;c.7462C>T;c.7411C>T;c.7345-1G>A;c.7012C>T;c.6946G>A;c.6900+1G>A;c.6859G>A;c.6781C>T;c.6770G>C;c.6752G>A;c.6724G>A;c.6724G>C;c.6670G>T;c.6656dupT;c.6573+1G>T;c.6527dupC;c.6218G>T;c.6205C>T;c.6190G>A;c.6187C>T;c.6127G>A;c.6127G>T;c.6118G>A;c.6110G>A;c.6109G>A;c.6101G>C;c.6100G>A;c.6091G>A;c.6081delC;c.6082G>A;c.6074delG;c.6022C>T;c.6017G>A;c.6007G>A;c.5932C>T;c.5924_5927delAACG;c.5821-1G>A;c.5797C>T;c.5701-1G>T;c.5532+1G>A;c.5443G>A;c.5425-1G>C;c.5344G>A;c.5287C>T;c.5261dupC;c.5096C>T;c.5052+1G>A;c.5048_5051dupGAAA;c.5047C>T;c.5015delA;c.4980+1G>C;c.4919delG;c.4888C>T;c.4871delC;c.4783G>C;c.4767delA;c.4568delC;c.4466delG;c.4373C>T;c.4233delT;c.4119+1G>T;c.4039G>C;c.4027C>T;c.4011+1G>A;c.3971delT;c.3942dupG;c.3840delC;c.3831+1G>T;c.3751_3752insACCA;c.3631C>T;c.3504delC;c.3265C>T;c.3140-1G>A;c.2993-2A>G;c.2710+2T>C;c.2607_2608delCC;c.2471dupG;c.2318_2321dupCTGA;c.2223_2226dupTGGA;c.2005C>T;c.1781-1G>C;c.1732C>T;c.1637-1G>A;c.1573C>T;c.933C>A;c.887delG;c.751C>T;c.706C>T;c.682+1G>A;c.553C>T;c.497dupA;c.425A>G;c.409C>T;c.336C>G;c.58C>T;c.1A>G

Myasthenic syndrome, congenital, type 5

Descripción enfermedad:
Congenital myasthenic syndromes (CMS) are a group of inherited disorders affecting the neuromuscular junction (NMJ). Patients present clinically with onset of variable muscle weakness between infancy and adulthood. These disorders have been classified according to the location of the defect: presynaptic, synaptic, and postsynaptic. Endplate acetylcholinesterase deficiency is an autosomal recessive congenital myasthenic syndrome characterized by a defect within the synapse at the neuromuscular junction (NMJ). Mutations in COLQ result in a deficiency of acetylcholinesterase (AChE), which causes prolonged synaptic currents and action potentials due to extended residence of acetylcholine in the synaptic space. Treatment with ephedrine may be beneficial; AChE inhibitors and amifampridine should be avoided (Engel et al., 2015).

c.1321A>G;c.1228C>T;c.1082delC;c.943C>T;c.844A>T;c.788dupC;c.718G>T;c.679C>T;c.640G>T;c.529-2A>G;c.506C>G;c.393+1G>A;c.157dupC

Carbamoylphosphate synthetase 1 deficiency

Descripción enfermedad:
Carbamoylphosphate synthetase deficiency type 1 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the CPS1 gene located on chromosomal region 2q35. The age of onset is infantile. This disease is characterized by congenital hyperammonemia and defective citrulline synthesis. The prevalence is 1:800,000 newborn in Japan.

c.144+1G>A;c.148C>T;c.254+1G>T;c.319delA;c.505G>T;c.612_613delGA;c.729+1G>C;c.730C>T;c.781G>T;c.816delG;c.1028A>G;c.1104+1G>A;c.1105-1G>T;c.1205C>A;c.1330G>C;c.1431dupC;c.1547delG;c.1649C>T;c.1778G>A;c.1930C>T;c.1931G>C;c.1944delC;c.2179C>T;c.2211-1G>T;c.2245delC;c.2357G>A;c.2377C>T;c.2409+1G>A;c.2410-1G>T;c.2425C>A;c.2447A>G;c.2827_2828delAT;c.2901_2913delCTACAATGGTCAG;c.2963G>A;c.3159+1G>A;c.3203delA;c.3393delC;c.3574delA;c.3577-2A>G;c.3802C>T;c.4020+2T>A;c.4021-2A>T;c.4021-1G>C;c.4074delC;c.4119+2T>C;c.4292+2T>C

Carnitine palmitoyltransferase type 1A deficiency, hepatic

Descripción enfermedad:
Carnitine palmitoyl transferase 1A deficiency follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the CPT1A gene located on chromosomal region 11q13.2. The age of onset is neonatal/infantile. This disease is characterized by recurrent attacks of fasting-induced hypoketotic hypoglycemia and risk of liver failure. The prevalence is 1.3:1,000 newborn.

c.2129G>A;c.2071C>T;c.2028+2T>G;c.1997_1998insAAAA;c.1876-1G>A;c.1876-1G>C;c.1737C>A;c.1711C>T;c.1600delC;c.1576-2A>G;c.1575+1G>A;c.1494T>A;c.1494T>G;c.1459-1G>A;c.1458+1G>A;c.1436C>T;c.1425G>A;c.1393G>T;c.1386delC;c.1361A>G;c.1348_1352+4delGACAGGTAC;c.1339C>T;c.1298delA;c.1241C>T;c.1216C>T;c.1163+2T>C;c.1163+1G>A;c.1079A>G;c.967+2T>C;c.967+1G>A;c.948delG;c.919C>T;c.772-1G>A;c.772-2A>G;c.771+1G>C;c.727C>T;c.694-2A>G;c.693+1G>C;c.693+1G>T;c.548_549delTG;c.478C>T;c.335_336delCC;c.298C>T;c.282-1G>A;c.281+1G>A;c.222C>A;c.186G>A;c.96T>G

Carnitine palmitoyltransferase type 2 deficiency, lethal neonatal; Carnitine palmitoyltransferase type 2 deficiency, infantile

Descripción enfermedad:
Carnitine palmitoyltransferase deficiency, type 2, lethal neonatal form follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the CPT2 gene located on chromosomal region 1p32. The age of onset is neonatal/infantile. This disease is characterized by a severe fasting intolerance leading to metabolic derangements of hypoketotic hypoglycemia, resulting in coma and seizures, and hepatic encephalopathy leading to liver failure. The prevalence is <1:1,000,000.

c.38delG;c.98delA;c.110_111dupGC;c.149C>A;c.338C>T;c.359A>G;c.370C>T;c.401_404delTTAT;c.452G>A;c.464dupT;c.520G>A;c.520G>T;c.606T>A;c.638A>G;c.670delA;c.680C>T;c.725_726delAC;c.748_749delAA;c.852delC;c.879_880delTG;c.886C>T;c.1046dupA;c.1046_1047delAC;c.1053G>A;c.1148T>A;c.1237C>T;c.1239_1240delGA;c.1324dupA;c.1345C>T;c.1345delCinsTA;c.1348A>T;c.1359_1362delAGAA;c.1360G>T;c.1369A>T;c.1375C>T;c.1414C>T;c.1432C>T;c.1436A>T;c.1437C>G;c.1446_1447delAG;c.1545_1548delCTTT;c.1614C>A;c.1645+2T>G;c.1737delC;c.1784delC;c.1883A>C;c.1891C>T;c.1925_1937delAGGCCTTAGAAGA

Retinitis pigmentosa, type 12; Leber congenital amaurosis, type 8

Descripción enfermedad:
Retinitis pigmentosa type 12 and Leber congenital amaurosis type 8 follow an autosomal recessive pattern of inheritance and are caused by pathogenic variants in the CRB1 gene located on chromosomal region 1q31-q32.1. Retinitis pigmentosa type 12 is characterized by night blindness, peripheral visual field impairment and over time loss of central visionm, and its prevalence is 1-5:10,000. Leber congenital amaurosis, with a neonatal/infantile age of onset, comprises a group of early-onset childhood retinal dystrophies characterized by vision loss, nystagmus, and severe retinal dysfunction. Patients usually present at birth with profound vision loss and pendular nystagmus. Other clinical findings of this disease may include high hypermetropia, photodysphoria, oculodigital sign, keratoconus, cataracts, and a variable appearance to the fundus.

c.257_258dupTG;c.498_506delAATTGATGG;c.584G>T;c.613_619delATAGGAA;c.799_800delGCinsA;c.807dupA;c.998G>A;c.1180T>C;c.1182C>A;c.1183G>T;c.1459dupT;c.1576C>T;c.1612_1613insCTTA;c.2220dupC;c.2222T>C;c.2234C>T;c.2290C>T;c.2330_2336delCAAACTC;c.2401A>T;c.2416G>T;c.2501G>A;c.2548G>A;c.2688T>A;c.2783G>A;c.2843G>A;c.2869C>T;c.2983G>T;c.3055_3059dupTATAT;c.3122T>C;c.3172G>T;c.3299T>C;c.3299T>G;c.3307G>A;c.3383delT;c.3419T>A;c.3541T>C;c.3542dupG;c.3676G>T;c.3988delG;c.3997G>T;c.4121_4130delCAACTCAGGG

Osteogenesis imperfecta, type 7

Descripción enfermedad:
Osteogenesis imperfecta, type 7 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the CRTAP gene located on chromosomal region 3p22.3. The age of onset is variable. This disease is characterized by increased bone fragility, low bone mass, and susceptibility to bone fractures with variable severity. The prevalence is 6:100,000-7:100,000.

c.118_133delGAGCTGATGCCGCTCGinsTACCC;c.118G>T;c.180G>A;c.471+2C>A;c.561T>G;c.634C>T;c.826C>T

Nephropathic cystinosis

Descripción enfermedad:
Nephropathic cystinosis follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the CTNS gene located on chromosomal region 17p13. The age of onset is neonatal/infantile. This disease is characterized by hypothyroidism, insulin-dependent diabetes, hepatosplenomegaly with portal hypertension, and muscle, cerebral and ocular involvement, caused by cystine deposits in various organs. The prevalence is 1:100,000-1:200,000.

c.-19-1G>A;c.18_21delGACT;c.40delC;c.61+1G>A;c.62-2A>G;c.91dupG;c.120delC;c.206_210delTCCTT;c.225+1G>A;c.251delA;c.257_258delCT;c.283G>T;c.292dupA;c.320_323delATCA;c.323delA;c.329G>T;c.329+2T>C;c.357_360delCAGC;c.382C>T;c.397_398delAT;c.414G>A;c.416C>T;c.506G>A;c.516dupC;c.519_520delCA;c.544T>C;c.561+1delG;c.589G>A;c.646dupA;c.681+2T>C;c.682-1G>A;c.696_697dupCG;c.696dupC;c.734G>A;c.751_754delACCAinsCG;c.829dupA;c.853-3C>G;c.853-2A>G;c.853-1G>A;c.870C>G;c.890G>A;c.926dupG;c.922G>A;c.969C>G;c.971-12G>A;c.1015G>A

Ceroid lipofuscinosis, neuronal, type 10

Descripción enfermedad:
Neuronal ceroid lipofuscinosis, type 10 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the CTSD gene located on chromosomal region 11p15.5. The age of onset is adult. This disease is characterized by dementia, seizures and loss of motor capacities, and sometimes associated with visual loss caused by retinal degeneration. The prevalence is 2:100,000-4:100,000 newborn.

c.1155_1169dupGGGCGACGTCTTCAT;c.1149G>C;c.764dupA;c.685T>A;c.446G>T;c.299C>T;c.268dupC

Pycnodysostosis

Descripción enfermedad:
Pycnodysostosis follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the CTSK gene located on chromosomal region 1q21. The age of onset is variable. This disease is characterized by osteosclerosis, short stature or dwarfism, acroosteolysis of the distal phalanges, fragile bones associated with spontaneous fractures and dysplasia of the clavicles. The prevalence is 1/1,000,000 to 9/1,000,000.

c.990A>G;c.934C>G;c.934C>T;c.926T>C;c.876G>A;c.784+1G>A;c.721C>T;c.679_680insAA;c.669delG;c.648delC;c.618+1G>A;c.568C>T;c.436G>C;c.426delT;c.400-1G>C;c.395dupA;c.289_290delCT;c.236G>A;c.213T>A;c.154A>T;c.121-2A>G;c.120+1G>A;c.48delG;c.3G>A

Chronic granulomatous disease, autosomal recessive, due to deficiency of CYBA

Descripción enfermedad:
Chronic granulomatous disease is a genetically heterogeneous immunodeficiency disorder resulting from an inability of phagocytes to kill microbes that they have ingested. This impairment in killing is caused by any of several defects in the NADPH oxidase enzyme complex which generates the microbicidal 'respiratory burst.'

c.354C>A;c.7C>T

Chronic granulomatous disease, X-linked

Descripción enfermedad:
Chronic granulomatous disease is a genetically heterogeneous immunodeficiency disorder resulting from an inability of phagocytes to kill microbes that they have ingested. This impairment in killing is caused by any of several defects in the phagocyte NADPH oxidase (phox) complex, which generates the microbicidal 'respiratory burst' (Dinauer et al., 2001; Johnston, 2001).

c.23_26dupAGGG;c.80_83delTCTG;c.85delT;c.90_92delCCGinsGGT;c.141+1G>T;c.170C>A;c.210dupA;c.217C>T;c.271C>T;c.301C>T;c.302A>G;c.337+1G>T;c.343C>T;c.388delC;c.448G>T;c.469C>T;c.483+1G>T;c.484-2A>T;c.532A>C;c.565_568delATTA;c.607G>T;c.625C>T;c.626A>G;c.676C>T;c.731G>C;c.742dupA;c.781C>T;c.868C>T;c.898-2A>C;c.907C>A;c.907C>T;c.911C>G;c.960delA;c.1006G>T;c.1011G>A;c.1140dupG;c.1166G>C;c.1169C>T;c.1223G>A;c.1244C>A;c.1272G>A;c.1315-1G>A;c.1449G>A;c.1498G>C;c.1499A>G;c.1573delA;c.1609T>C;c.1618delG

Glaucoma, primary congenital, type 3A

Descripción enfermedad:
Primary congenital glaucoma is the most common type of childhood glaucoma, with autosomal recessive inheritance and an incidence ranging from 1 in 30,000 to 1 in 1,250. Signs of the disease include early onset (birth to 3 years of age), increased intraocular pressure, increased corneal diameter, enlarged globe, Haab striae (breaks in Descemet membrane), corneal edema, and optic nerve head cupping. Congenital glaucoma is a chronic disease and a serious cause of blindness worldwide (Azmanov et al., 2011).

c.1405C>T;c.1345delG;c.1330C>T;c.1302G>A;c.1200_1209dupTCATGCCACC;c.1159G>A;c.1064_1076delGAGTGCAGGCAGA;c.1063_1075delCGAGTGCAGGCAG;c.868dupC;c.830delT;c.535delG;c.171G>A;c.2T>C

Cerebrotendinous xanthomatosis

Descripción enfermedad:
Cerebrotendinous xanthomatosis is a rare inherited lipid-storage disease characterized clinically by progressive neurologic dysfunction (cerebellar ataxia beginning after puberty, systemic spinal cord involvement and a pseudobulbar phase leading to death), premature atherosclerosis, and cataracts. Large deposits of cholesterol and cholestanol are found in virtually every tissue, particularly the Achilles tendons, brain, and lungs. Cholestanol, the 5-alpha-dihydro derivative of cholesterol, is enriched relative to cholesterol in all tissues. The diagnosis can be made by demonstrating cholestanol in abnormal amounts in the serum and tendon of persons suspected of being affected. Plasma cholesterol concentrations are low normal in CTX patients. Dotti et al. (2001) examined the ophthalmologic findings of 13 CTX patients. In addition to cataracts, which were found in all cases, optic disc pallor was identified in 6 of the patients. Premature retinal senescence was also observed.In a tabular presentation, Moghadasian et al. (2002) compared and contrasted CTX with 2 other lipid disorders with certain similarities and clinical course: familial hypercholesterolemia (143890) and sitosterolemia (210250).

c.11_20dupTGGGCTGCGC;c.5dupC;c.73delG;c.256-2A>G;c.256-1G>T;c.305delC;c.355delC;c.373_379delCCAGTAC;c.380G>A;c.446+1G>A;c.446+1G>T;c.475C>T;c.526delG;c.583G>T;c.646+1G>C;c.646+2T>C;c.647-1G>T;c.666_678delCGAGAAACGCATT;c.691C>T;c.745C>T;c.752C>A;c.779G>A;c.808C>T;c.819delT;c.844+1G>A;c.845-2A>G;c.845-1G>A;c.847A>T;c.850A>T;c.863delA;c.886C>T;c.944_948delTGGCC;c.1016C>T;c.1072C>T;c.1180_1181delCT;c.1183C>T;c.1184G>A;c.1184+1G>A;c.1185-2A>C;c.1185-2A>T;c.1185-1G>A;c.1185-1G>T;c.1214G>A;c.1222G>T;c.1263+1G>A;c.1263+2T>C;c.1264-2A>G;c.1264-1G>A;c.1381C>T;c.1415G>C;c.1420C>T;c.1421G>A;c.1435C>G;c.1435C>T;c.1477-2A>C;c.1573C>T

Maple syrup urine disease, type 2

Descripción enfermedad:
Maple syrup urine disease, type 2 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the DBT gene located on chromosomal region 1p21.2. The age of onset in neonatal/infantil. This disease is characterized by a maple syrup odor to the urine, deficient diet, lethargy and focal dystonia, followed by progressive encephalopathy and central respiratory failure if not treated. The prevalence is 1-5/10,000.

c.1448G>T;c.1355A>G;c.1281+1G>A;c.1165_1166delAC;c.1033G>A;c.1017+1delG;c.939G>C;c.901C>T;c.871C>T;c.827T>G;c.773-2A>G;c.772+1G>A;c.731delC;c.725C>G;c.670G>T;c.634C>T;c.581C>G;c.555+1G>A;c.434-1G>A;c.433+1G>T;c.360delA;c.360dupA;c.339_345delTTATGAT;c.294C>G;c.272_275delCAGT;c.251G>A;c.141_142delTA;c.126T>G;c.75_76delAT;c.51+1G>T

Omenn syndrome; Severe combined immunodeficiency, Athabascan type

Descripción enfermedad:
Omenn syndrome and Athabascan type severe combined immunodeficiency follow an autosomal recessive pattern of inheritance and are caused by pathogenic variants in the DCLRE1C gene located on chromosomal region 10p13. Omenn syndrome has an early age of onset and it is characterized by erythroderma, desquamation, alopecia, chronic diarrhea, failure to thrive, lymphadenopathy, and hepatosplenomegaly, associated with severe combined immunodeficiency. The age of onset of Athabascan type severe combined immunodeficiency is neonatal/infantile and it is characterized by severe and recurrent infections, diarrhea, failure to thrive, and cell sensitivity to ionizing radiation. The prevalence is 1-9/1,000,000.

c.1669dupA;c.1639G>T;c.1558dupA;c.1350_1356delAGATTGT;c.780+1delG;c.597C>A;c.403G>A;c.241C>T;c.194C>T;c.103C>G;c.2T>C

Xeroderma pigmentosum, complementation group E

Descripción enfermedad:
Xeroderma pigmentosum complementation group E follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the DDB2 gene located on chromosomal region 11p12-p11. The age of onset is variable. This disease is characterized by mild xeroderma pigmentosum symptoms and no neurological abnormalities. The prevalence is 1/1,000,000.

c.730A>G;c.818G>A;c.919G>T;c.937C>T

Smith-Lemli-Opitz syndrome

Descripción enfermedad:
Smith-Lemli-Opitz syndrome follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the DHCR7 gene located on chromosomal region 11q13.4. The age of onset is neonatal/infantile. This disease is characterized by multiple congenital anomalies, intellectual deficit, and behavioral problems. The prevalence is 1/20,000 to 1/40,000 newborn.

c.1426T>C;c.1396G>A;c.1342G>A;c.1337G>A;c.1328G>A;c.1228G>A;c.1222T>C;c.1210C>T;c.1139G>A;c.1138T>C;c.1057delG;c.1055G>A;c.1054C>T;c.976G>T;c.964-1G>C;c.964-1G>T;c.963+2T>G;c.963+1G>T;c.939G>A;c.934_935delGT;c.915C>G;c.907G>A;c.906C>G;c.894C>A;c.870G>A;c.866C>T;c.862G>A;c.858G>A;c.841G>A;c.839A>G;c.832-1G>C;c.831+2T>A;c.804delT;c.744G>T;c.740C>T;c.730G>A;c.725G>A;c.724C>T;c.627-1G>A;c.626+1G>C;c.626+1G>T;c.506C>T;c.470T>C;c.461C>G;c.461C>T;c.453G>A;c.452G>A;c.440G>A;c.413-1G>A;c.413-2A>G;c.356A>T;c.322-2A>G;c.292C>T;c.278C>T;c.151C>T;c.111G>A;c.99-1G>C;c.89G>C;c.82C>T;c.16C>T;c.3G>A;c.1A>G

Retinitis pigmentosa, type 59

Descripción enfermedad:
Retinitis pigmentosa, type 59 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the DHDDS gene located on chromosomal region 1p36.11. The age of onset is variable. This disease is characterized by night blindness (nyctalopia), peripheral visual field impairment and over time loss of central vision. The prevalence is 1/10,000 to 5/10,000.

c.124A>G;c.192G>A;c.330delA;c.998C>G

Dihydrolipoamide dehydrogenase deficiency

Descripción enfermedad:
Dihydrolipoamide dehydrogenase deficiency E3 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the DLD gene located on chromosomal region 7q31-q32. The age of onset is neonatal/infantile. This disease is characterized by poor feeding, lethargy, vomiting and a maple syrup odor in the cerumen (and later in urine) noted soon after birth, followed by progressive encephalopathy and central respiratory failure if untreated. The prevalence is 1/1,000,000 to 9/1,000,000.

c.39+1G>A;c.82delT;c.104dupA;c.105delC;c.105_106insA;c.105C>G;c.112C>T;c.118+1G>T;c.140T>C;c.198+1G>A;c.199-1G>A;c.214A>G;c.223dupA;c.268-2A>G;c.633dupA;c.685G>T;c.803_804delAG;c.865dupA;c.916_926delTGTGATGTACT;c.1081A>G;c.1123G>A;c.1178T>C;c.1236+1G>T;c.1429_1432delTGTG;c.1436A>T;c.1446_1447delAG;c.1463C>T;c.1483A>G

Fetal akinesia deformation sequence, type 3; Myasthenic syndrome, congenital, type 10

Descripción enfermedad:
The fetal akinesia deformation sequence (FADS) refers to a clinically and genetically heterogeneous constellation of features including fetal akinesia, intrauterine growth retardation, arthrogryposis, and developmental anomalies, including lung hypoplasia, cleft palate, and cryptorchidism (Vogt et al., 2009). It shows phenotypic overlap with the lethal form of multiple pterygium syndrome. Mutation in the DOK7 gene can also cause a form of congenital myasthenic syndrome (CMS10). Congenital myasthenic syndromes (CMS) are a group of inherited disorders affecting the neuromuscular junction (NMJ). Patients present clinically with onset of variable muscle weakness between infancy and adulthood. These disorders have been classified according to the location of the defect: presynaptic, synaptic, and postsynaptic. CMS10 is an autosomal recessive CMS resulting from a postsynaptic defect affecting endplate maintenance of the NMJ. Patients present with limb-girdle weakness in the first decade. Treatment with ephedrine or salbutamol may be beneficial; cholinesterase inhibitors should be avoided (Engel et al., 2015).

c.55-1G>T;c.331+1G>T;c.481G>A;c.513C>T;c.539G>C;c.548_551delTCCT;c.596delT;c.601C>T;c.957delC;c.1124_1127dupTGCC;c.1138dupG;c.1143dupC;c.1263dupC;c.1339_1342dupCTGG;c.1378dupC

Congenital disorder of glycosylation, type 1M

Descripción enfermedad:
Congenital disorder of glycosylation, type 1M (CDG1M) is a form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG1M is a very severe disease with death occurring in early life.

c.2T>C

Congenital disorder of glycosylation, type 1J; Myasthenic syndrome, congenital, type 13

Descripción enfermedad:
Congenital disorder of glycosylation, type 1J (CDG1J) follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the DPAGT1 gene located on chromosomal region 11q23.3. The age of onset is neonatal/infantile. This disease is characterized by severe psychomotor delay, seizures, hypotonia and dysmorphism (microcephaly, ocular exotropia, micrognathia and clinodactyly). The prevalence is below 1,000,000. Mutation in the DPAGT1 gene can also cause congenital myasthenic syndrome, type 13 (CMS13). CMS13 is an autosomal recessive neuromuscular disorder characterized by onset of proximal muscle weakness in the first decade. CMS13 is characterized by muscle weakness mostly affecting proximal limb muscles, minimal involvement of facial, ocular and bulbar muscles, and tubular aggregates present on muscle biopsy. Symptoms include difficulty walking and frequent falls. Younger patients show hypotonia and poor head control. Neurophysiological features indicate a disorder of neuromuscular transmission on electromyography.

c.980_981delCT;c.791T>G;c.699dupC;c.643+1G>A;c.358C>A;c.349G>A;c.324G>C;c.26dupT

Congenital disorder of glycosylation, type 1E

Descripción enfermedad:
Congenital disorder of glycosylation, type 1E (CDG1E) follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the DPM1 gene located on chromosomal region 20q13.13. The age of onset is neonatal/infantile. This disease is characterized by psychomotor delay, seizures, hypotonia, facial dysmorphism and microcephaly. The prevalence is below 1,000,000.

c.847T>C;c.784-1G>T;c.733delC;c.669-1G>A;c.331_343delGGAAACTACATCA;c.274C>G

Dihydropyrimidine dehydrogenase deficiency

Descripción enfermedad:
Dihydropyrimidine dehydrogenase deficiency follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the DPYD gene located on chromosomal region 1p22. This disease shows large phenotypic variability, ranging from no symptoms to a convulsive disorder with motor and mental retardation in homozygous patients. In people with severe dihydropyrimidine dehydrogenase deficiency, the disorder becomes apparent in infancy. These affected individuals have recurrent seizures (epilepsy), intellectual disability, a small head size (microcephaly), increased muscle tone (hypertonia), delayed development of motor skills such as walking, and autistic behaviors that affect communication and social interaction. The prevalence is unknow.
In addition, homozygous and heterozygous mutation carriers can develop severe toxicity after the administration of the antineoplastic drug 5-fluorouracil (5FU).

c.2921A>T;c.2767-1G>A;c.2754delT;c.2748delG;c.2680A>T;c.2622+1G>A;c.2589dupA;c.2554C>T;c.2335_2338delACCTinsGC;c.2286_2287insA;c.2275C>T;c.2135delC;c.2058+1G>C;c.2039dupT;c.2003delA;c.1970delC;c.1905+1G>A;c.1863G>A;c.1831G>T;c.1727delT;c.1681C>T;c.1679T>G;c.1671delA;c.1524+1G>A;c.1518delC;c.1379dupG;c.1340-2A>G;c.1339+1G>T;c.1316delG;c.1311delC;c.1243G>T;c.1109_1110delTA;c.1041_1042delTG;c.910delT;c.851-1G>C;c.763-2A>G;c.762+2T>C;c.680+1G>A;c.661G>T;c.523delT;c.483+1G>T;c.322-1G>C;c.299_302delTCAT;c.233+1G>T;c.232A>T;c.220C>T;c.208C>T;c.150+2T>A;c.127_134delAGAAATCC;c.61C>T

Miyoshi muscular dystrophy, type 1; Limb-girdle muscular dystrophy, type 2 (LGMD R2)

Descripción enfermedad:
Miyoshi muscular dystrophy, type 1 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the DYSF gene located on chromosomal region 2p13.3. The age of onset is young adulthood. This disease is characterized by weakness and atrophy in the distal lower extremity posterior compartment (gastrocnemius and soleus muscles) and is associated with difficulties in standing on tip toes. The prevalence is 1/1,000,000 to 9/1,000,000. Mutations in the DYSF gene can also cause muscular dystrophy, limb-girdle, autosomal recessive, type 2. This disease is characterized by an onset in late adolescence or early adulthood of slowly progressive, proximal weakness and atrophy of shoulder and pelvic girdle muscles. Cardiac and respiratory muscles are not involved. Hypertrophy of the calf muscles and highly elevated serum creatine kinase levels are frequently observed.

c.92-1G>A;c.110_111delAA;c.159G>A;c.167dupA;c.203_204delTGinsAT;c.240-1G>A;c.268C>T;c.334C>T;c.342delA;c.356delT;c.361C>T;c.386G>A;c.396_397delCC;c.404C>T;c.410delC;c.460+1G>A;c.622C>T;c.682dupC;c.706C>T;c.727A>G;c.757C>T;c.759+1G>C;c.797G>A;c.851C>T;c.853C>T;c.886G>T;c.888+1G>A;c.888+2T>A;c.889-2A>G;c.892_893delCT;c.922delG;c.951+1delG;c.951+2T>G;c.952-2A>G;c.991G>A;c.991G>T;c.1003-2A>G;c.1033+1G>A;c.1033+2T>C;c.1149+1G>A;c.1167delC;c.1225C>T;c.1264G>A;c.1273C>T;c.1277-2A>C;c.1350delC;c.1372G>A;c.1380+2T>C;c.1381-2A>G;c.1449+1G>A;c.1464C>A;c.1471dupA;c.1488dupA;c.1493G>A;c.1493+1G>A;c.1494-2A>G;c.1494-1G>A;c.1530delC;c.1544C>A;c.1480G>T;c.1576+1G>A;c.1481-1G>A;c.1517C>G;c.1577-2A>G;c.1577-1G>A;c.1609G>A;c.1674delA;c.1692+2T>A;c.1693-6T>A;c.1696delG;c.1696dupG;c.1717C>T;c.1762C>T;c.1812C>G;c.1867C>T;c.1888C>T;c.1906G>A;c.1915G>A;c.1927G>T;c.2010G>A;c.2217-2A>G;c.2217-1G>T;c.2302C>T;c.2344G>T;c.2365C>T;c.2378G>A;c.2409+1G>A;c.2426dupC;c.2426C>G;c.2550_2553delGACA;c.2548C>T;c.2697+1G>A;c.2698-2A>G;c.2826G>A;c.2833delG;c.2864+1G>A;c.2864+2T>A;c.2865-2A>C;c.2924_2928delAGACC;c.2923C>T;c.2929C>T;c.2948G>A;c.3051G>T;c.3085+1G>T;c.3085+2T>C;c.3095A>G;c.3105dupC;c.3166C>T;c.3167G>A;c.3191G>A;c.3229-2A>T;c.3284G>A;c.3361A>T;c.3381_3382delGT;c.3403-2A>G;c.3421_3422delAA;c.3483delC;c.3498_3499delTGinsAA;c.3498T>A;c.3531C>A;c.3532C>T;c.3558dupC;c.3566_3567delCT;c.3570_3571delTT;c.3571dupT;c.3655C>T;c.3695delC;c.3741C>A;c.3757-2A>G;c.3762delA;c.3824G>A;c.3827delT;c.3859G>T;c.3886C>T;c.3897+1G>A;c.3941C>G;c.3957+1delG;c.3957+2T>A;c.3969delA;c.4011delC;c.4042C>T;c.4144C>T;c.4162_4163delGT;c.4221+1G>C;c.4254dupC;c.4282C>T;c.4307G>A;c.4353C>G;c.4387+2T>A;c.4462C>T;c.4528-2A>G;c.4551G>A;c.4576G>T;c.4614delT;c.4701C>G;c.4802dupT;c.4843C>T;c.4873C>T;c.4909A>T;c.4911+1G>T;c.4989_4993delGCCCGinsCCCC;c.5003+1249G>T;c.5004-1G>A;c.5011G>T;c.5086G>T;c.5135delA;c.5139delT;c.5174+1G>A;c.5174+2T>C;c.5194C>T;c.5195G>A;c.5200C>T;c.5317+1G>A;c.5318A>G;c.5383C>T;c.5419C>T;c.5457+1G>A;c.5458-2A>C;c.5458-1G>A;c.5467C>T;c.5531dupC;c.5546G>A;c.5546+1G>T;c.5546+2T>A;c.5614G>T;c.5626G>A;c.5642G>A;c.5642+1G>A;c.5646G>A;c.5711delG;c.5724G>A;c.5761C>T;c.5784+1G>A;c.5785-7G>A;c.5785-1G>C;c.5815_5816delAG;c.5830C>T;c.5884+1G>A;c.5885-1G>C;c.5938A>T;c.5953_5956delCAGC;c.6001C>T;c.6021G>A;c.6025C>T;c.6063+1G>A;c.6064-1G>C;c.6096dupA;c.6099_6106dupGAGTGAGC;c.6109G>T;c.6139G>T;c.6174-2A>G;c.6241C>T;c.6251G>A;c.6252G>A

Ectodermal dysplasia, type 1, hypohidrotic, X-linked

Descripción enfermedad:
Hypohidrotic ectodermal dysplasia, type 1, hypohidrotic, X-linked follows an X-linked pattern of inheritance and is caused by pathogenic variants in the EDA gene located on chromosomal region Xq12-q13.1. The age of onset is neonatal/infantile. This disease is characterized by malformation of ectodermal structures such as skin, hair, teeth and sweat glands. The prevalence is 1/5,000 to 1/10,000 newborns.

c.2T>C;c.67C>T;c.164T>A;c.181T>C;c.183C>G;c.187G>A;c.193C>G;c.245delG;c.396+1G>A;c.396+2T>C;c.396+2T>G;c.457C>T;c.463C>T;c.466C>T;c.467G>A;c.467G>T;c.502+1G>A;c.527-2A>T;c.573_574insT;c.599dupC;c.628G>T;c.671G>C;c.676C>T;c.706+1G>A;c.707-1G>A;c.730C>T;c.755A>T;c.764G>A;c.766C>T;c.769G>C;c.776C>A;c.794A>G;c.809delT;c.822delG;c.822G>A;c.822G>T;c.826C>T;c.827G>T;c.865C>T;c.866G>A;c.871G>A;c.872G>A;c.895G>A;c.902A>G;c.911A>C;c.917A>G;c.922G>T;c.923A>G;c.961G>T;c.991C>T;c.1013C>T;c.1045G>A;c.1067C>T;c.1072C>G;c.1094T>C;c.1133C>T;c.1137C>A;c.1144G>A

Leukoencephalopathy with vanishing white matter

Descripción enfermedad:
Vanishing white matter leukodystrophy is an autosomal recessive neurologic disorder characterized by variable neurologic features, including progressive cerebellar ataxia, spasticity, and cognitive impairment associated with white matter lesions on brain imaging. The age at onset can range from early infancy to adulthood. Rapid neurologic deterioration can occur following minor head trauma. Female mutation carriers may develop ovarian failure, manifest as primary amenorrhea or as secondary amenorrhea lasting more than 6 months, associated with elevated gonadotropin levels at age less than 40 years (Van der Knaap et al., 1998; Schiffmann et al., 1997).

c.166T>G;c.167T>G;c.241G>A;c.271A>G;c.338G>A;c.380T>C;c.583C>T;c.584G>A;c.808G>C;c.896G>A;c.925G>C;c.944G>A;c.1010A>G;c.1016G>A;c.1030C>T;c.1157G>T;c.1882T>C;c.1946T>C

Emery-Dreifuss muscular dystrophy, type 1, X-linked

Descripción enfermedad:
Emery-Dreifuss muscular dystrophy, type 1, X-linked follows an X-linked pattern of inheritance and is caused by pathogenic variants in the EMD gene located on chromosomal region Xq28.  This is a condition that primarily affects muscles used for movement (skeletal muscles) and the heart (cardiac muscle). Among the earliest features of this disorder are joint deformities called contractures. Contractures restrict the movement of certain joints, most often the elbows, ankles, and neck, and usually become noticeable in early childhood. Most affected individuals also experience muscle weakness and wasting that worsen slowly over time, beginning in muscles of the upper arms and lower legs and later also affecting muscles in the shoulders and hips. Almost all people with Emery-Dreifuss muscular dystrophy develop heart problems by adulthood. The X-linked type of this disorder affects an estimated 1 in 100,000 people.

c.1A>G;c.3G>A;c.82+1G>T;c.83-2A>G;c.103G>T;c.123C>A;c.130C>T;c.153dupC;c.184dupT;c.187+1G>T;c.239_240insT;c.251_255delTCTAC;c.266-2A>G;c.355C>T;c.419T>A;c.430G>T;c.450-2A>G;c.484C>T;c.512C>A;c.547C>A;c.548C>A;c.600G>A;c.607delC;c.621delG;c.631_635delCGTGC;c.650_654dupTGGGC;c.674_678delTCTGG

Trichothiodystrophy, type 1

Descripción enfermedad:
Trichothiodystrophy (TTD), type 1 is a heterogeneous group of disorders that follows an autosomal recessive pattern of inheritance. It is caused by pathogenic variants in the ERCC2 gene located on chromosomal region 19q13.32. The age of onset is neonatal or infantile. This disease, with variable clinical expression, is characterized by brittle and fragile hair, often combined with growth retardation and intellectual deficit, congenital ichthyosis and nail abnormalities, among other symptoms. About half of the patients with TTD exhibit marked photosensitivity.

c.2230_2233dupCTAG;c.2176C>T;c.2164C>T;c.2092C>T;c.2048G>A;c.2047C>T;c.2046+1G>T;c.2041G>A;c.2005delA;c.1972C>T;c.1906C>T;c.1847G>C;c.1846C>T;c.1703_1704delTT;c.1666-2A>T;c.1621A>C;c.1454T>C;c.1381C>G;c.1354C>T;c.1308-1G>A;c.950-2A>G;c.949+1G>A;c.719-1G>A;c.594+2_594+5delTGAG;c.567G>A;c.335G>A;c.183+2T>A

Trichothiodystrophy, type 2

Descripción enfermedad:
Trichothiodystrophy (TTD), type 2 is a heterogeneous group of disorders that follows an autosomal recessive pattern of inheritance. It is caused by pathogenic variants in the ERCC3 gene located on chromosomal region 2q14.3. The age of onset is neonatal or infantile. This disease, with variable clinical expression, is characterized by brittle and fragile hair, often combined with growth retardation and intellectual deficit, congenital ichthyosis and nail abnormalities, among other symptoms. About half of the patients with TTD exhibit marked photosensitivity.

c.1858delG;c.1757_1758delAG;c.1757delA;c.1633C>T;c.1421dupA;c.1273C>T;c.355A>C;c.325C>T;c.296T>C

Cerebrooculofacioskeletal syndrome, type 3

Descripción enfermedad:
Cerebrooculofacioskeletal syndrome type 3, also known as COFS syndrome, follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ERCC5 gene located on chromosomal region 13q33.1. COFS syndrome is characterized by prenatal onset of arthrogryposis, microcephaly and growth failure. Postnatal features include severe developmental delay, congenital cataracts (in some), and marked UV sensitivity of the skin. Survival beyond 6 years of age is rare. The prevalence is below 1/1,000,000.

c.83C>A;c.88+2T>C;c.215C>A;c.381-2A>G;c.406C>T;c.464dupA;c.526C>T;c.787C>T;c.1115_1118delGGAA;c.1173dupT;c.1494delA;c.2144dupA;c.2353C>T;c.2375C>T;c.2573T>C;c.2678+1G>A;c.2751delA;c.2766dupA;c.2878G>T;c.2904G>C;c.2929_2930delCT

Roberts syndrome

Descripción enfermedad:
Roberts syndrome follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ESCO2 gene located on chromosomal region 8p21.1. The age of onset is neonatal/infantile. This disease is characterized by pre- and postnatal growth retardation, severe symmetric limb reduction defects, craniofacial anomalies and severe intellectual deficit.

c.252_253delAT;c.294_297delGAGA;c.296_297dupGA;c.307_311delAAAGA;c.308_309delAA;c.417dupA;c.505C>T;c.604C>T;c.745_746delGT;c.751dupG;c.760delA;c.760dupA;c.764_765delTT;c.876_879delCAGA;c.879_880delAG;c.894delAinsTTTTAT;c.911dupA;c.955+2_955+5delTAAG;c.1111dupA;c.1111_1112insG;c.1131+1G>A;c.1132-7A>G;c.1263+1G>C;c.1269G>A;c.1461_1462delAG;c.1597dupT;c.1615T>G;c.1674-2A>G

Glutaric acidemia, type 2A

Descripción enfermedad:
Glutaric acidemia, type 2A follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ETFA gene located on chromosomal region 15q23-q25. The age of onset is variable. This disease is characterized by clinically heterogeneous symptoms ranging from a severe neonatal presentation with metabolic acidosis, cardiomyopathy and liver disease, to a mild childhood/adult disease with episodic metabolic decompensation, muscle weakness, and respiratory failure.

c.797C>T;c.667C>T;c.625C>T;c.470T>G;c.346G>A

Glutaric acidemia, type 2B

Descripción enfermedad:
Glutaric acidemia, type 2B follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ETFB gene located on chromosomal region 19q13.3. The age of onset is variable. This disease is characterized by clinically heterogeneous symptoms ranging from a severe neonatal presentation with metabolic acidosis, cardiomyopathy and liver disease, to a mild childhood/adult disease with episodic metabolic decompensation, muscle weakness, and respiratory failure.

c.887_889delAGA;c.764G>A;c.655G>A;c.551_552insG;c.334C>T;c.278_279insG

Glutaric acidemia, type 2C

Descripción enfermedad:
Glutaric acidemia, type 2C follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ETFDH gene located on chromosomal region 4q32-q35. The age of onset is variable. This disease is characterized by clinically heterogeneous symptoms disease, to a mild childhood/adult disease with episodic metabolic decompensation, muscle weakness, and respiratory failure.

c.2T>C;c.51dupT;c.121C>T;c.157A>T;c.175+1G>C;c.250G>A;c.302_303dupGT;c.380T>A;c.380T>C;c.413T>G;c.462C>G;c.524G>A;c.524G>T;c.560C>T;c.1001T>C;c.1073G>A;c.1130T>C;c.1234G>T;c.1285+1G>A;c.1366C>T;c.1367C>T;c.1448C>T;c.1570_1571delCT;c.1601C>T;c.1809G>A;c.1823delG;c.1832G>A

Ethylmalonic encephalopathy

Descripción enfermedad:
Ethylmalonic encephalopathy follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the ETHE1 gene located on chromosomal region 19q13.31. The age of onset is neonatal/infantile. This disease is characterized by elevated excretion of ethylmalonic acid with recurrent petechiae, orthostatic acrocyanosis and chronic diarrhoea associated with neurodevelopmental delay, psychomotor regression and hypotonia with brain magnetic resonance imaging abnormalities. The prevalence is below 1/1,000,000, with total of 30 cases of patients reported worldwide, mainly for Mediterranean and Arab populations.

c.604dupG;c.602_603delCA;c.595+2T>G;c.592dupC;c.554T>G;c.505+1G>A;c.505+1G>C;c.505+1G>T;c.494A>G;c.488G>A;c.487C>G;c.487C>T;c.440_450delACAGCATGGCC;c.230delA;c.226+1G>T;c.221dupA;c.187C>T;c.131_132delAG;c.113A>G;c.66delC;c.34C>T;c.3G>T

Retinitis pigmentosa, type 25

Descripción enfermedad:
Retinitis pigmentosa, type 25 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the EYS gene located on chromosomal region 6q12. The age of onset is variable. This disease is characterized by night blindness (nyctalopia), peripheral visual field impairment and over time loss of central vision. The prevalence is 1/10,000 to 5/10,000.

c.9468T>A;c.9362_9365delCTCA;c.9349_9358delGTAAATATCG;c.9340_9341dupGG;c.9249_9250delCA;c.9099delT;c.8868C>A;c.8711_8718delCATGCAGA;c.8692_8695dupACAG;c.8632G>T;c.8471dupA;c.8439_8442dupTGCA;c.8218_8219delCA;c.8196_8200delCTTTC;c.8012T>A;c.7919G>A;c.7822C>T;c.7694delA;c.7654delG;c.7229-1G>A;c.7095T>G;c.7048delT;c.6976C>T;c.6937C>T;c.6794delC;c.6714delT;c.6545delA;c.6528C>A;c.6502G>T;c.6229_6238delGTTGATGCTT;c.6170delA;c.6137G>A;c.6102dupT;c.5928-3_5928-1delCAG;c.5928-2A>G;c.5857G>T;c.5757dupT;c.5408C>G;c.5202_5203delGT;c.5167_5168delTT;c.5014C>T;c.4957dupA;c.4829_4832delCATT;c.4610_4611delGA;c.4462_4469dupAGCCCCTC;c.4395_4402dupTCAAGAGG;c.4393dupG;c.4387delA;c.4350_4356delTATAGCT;c.4120C>T;c.4045C>T;c.3775C>T;c.3443+1G>T;c.2976T>A;c.2826_2827delAT;c.2620C>T;c.2259+1G>A;c.2194C>T;c.2137+1G>A;c.2055T>A;c.1750G>T;c.1673G>A;c.1345A>T;c.1211delA;c.1211dupA;c.1161delA;c.881C>G;c.571dupA;c.490C>T;c.232delT;c.179delT;c.103C>T

Hemophilia A

Descripción enfermedad:
Hemophilia A follows an X-linked pattern of inheritance and is caused by pathogenic variants in the F8 gene located on chromosomal region Xq28. The age of onset is neonatal/infantile. This disease is characterized by spontaneous or prolonged hemorrhages due to factor VIII deficiency. The prevalence is 1/4,000 to 1/ 5,000 male newborns.

c.7033_7040delTGCGAGGC;c.7034G>A;c.7031G>A;c.7030G>A;c.7030G>T;c.7021G>T;c.7016G>T;c.7012delC;c.6997delG;c.6996G>A;c.6995G>C;c.6988delC;c.6986C>T;c.6977G>A;c.6977G>T;c.6976C>G;c.6976C>T;c.6968G>A;c.6967C>T;c.6956C>T;c.6955C>T;c.6914_6918delATCAA;c.6915delT;c.6905T>C;c.6904T>G;c.6901-2A>G;c.6900+1G>A;c.6887delA;c.6870G>A;c.6869G>T;c.6857_6867delATGGCCATCAG;c.6865C>T;c.6842T>C;c.6839T>C;c.6836T>C;c.6836T>G;c.6825T>A;c.6804delA;c.6797delG;c.6797G>A;c.6794_6795delAG;c.6796G>A;c.6794A>G;c.6780_6788delAGGAGTAAC;c.6786_6787insCAA;c.6760delC;c.6760C>T;c.6752T>A;c.6746T>G;c.6744G>T;c.6743G>C;c.6740_6741delAG;c.6738delA;c.6739G>T;c.6699delG;c.6683G>A;c.6683G>T;c.6682C>G;c.6682C>T;c.6631G>C;c.6574+5G>C;c.6574+3A>C;c.6574+1G>A;c.6574+1G>T;c.6565_6566delGA;c.6554T>C;c.6551A>T;c.6548T>G;c.6545G>A;c.6544C>G;c.6544C>T;c.6537C>G;c.6533G>A;c.6533G>T;c.6532C>T;c.6520C>G;c.6518C>T;c.6515C>A;c.6515C>G;c.6506G>A;c.6501delC;c.6497delG;c.6496C>T;c.6494delC;c.6489delT;c.6488T>G;c.6482C>A;c.6482C>T;c.6477delT;c.6469_6470delAA;c.6464_6465delAA;c.6465delA;c.6449A>T;c.6430-3C>G;c.6412_6413delTC;c.6413C>A;c.6404G>C;c.6403C>T;c.6371A>G;c.6360T>G;c.6278A>G;c.6273+1G>A;c.6269T>A;c.6263C>T;c.6253G>T;c.6250A>T;c.6243G>C;c.6242G>C;c.6239C>T;c.6213A>T;c.6194G>A;c.6193T>C;c.6136dupA;c.6134G>T;c.6130delC;c.6120T>A;c.6116-2A>G;c.6115+6T>A;c.6115+4A>G;c.6115+3G>T;c.6115+2T>C;c.6115+1G>A;c.6113A>G;c.6107A>G;c.6103G>A;c.6099delT;c.6089dupG;c.6084delG;c.6078_6079delTG;c.6070dupC;c.6049delG;c.6046C>G;c.6046C>T;c.6037G>A;c.6016G>T;c.5999G>C;c.5964_5967dupGGAG;c.5960_5961delAA;c.5961delA;c.5953delC;c.5954G>C;c.5953C>T;c.5939A>C;c.5938C>T;c.5936G>T;c.5934T>G;c.5923dupA;c.5924T>A;c.5914_5915delAT;c.5900G>A;c.5894G>T;c.5888T>C;c.5884T>G;c.5882G>A;c.5881T>A;c.5879G>A;c.5879G>T;c.5878C>T;c.5869C>T;c.5861_5866delCTCAGG;c.5853A>C;c.5833A>G;c.5825G>T;c.5822A>G;c.5821A>G;c.5816C>A;c.5766C>A;c.5752delT;c.5721C>G;c.5719dupA;c.5719A>T;c.5712G>C;c.5710G>A;c.5697delC;c.5696dupT;c.5689_5690delCT;c.5686G>C;c.5680G>A;c.5677C>T;c.5675dupT;c.5674G>A;c.5622dupT;c.5618C>G;c.5600A>G;c.5593G>A;c.5593G>T;c.5558C>T;c.5533A>C;c.5530C>T;c.5526G>A;c.5479A>T;c.5443C>T;c.5422C>T;c.5408C>A;c.5399G>A;c.5398C>G;c.5398C>T;c.5348_5357delGAGCAGAAGT;c.5345T>G;c.5343T>A;c.5339C>T;c.5337delG;c.5336G>A;c.5330T>C;c.5325G>C;c.5323T>G;c.5321A>T;c.5308G>A;c.5305G>A;c.5301C>A;c.5291A>G;c.5269delT;c.5269T>C;c.5254delG;c.5251A>T;c.5243delA;c.5227_5228delAG;c.5220-1G>A;c.5183A>G;c.5167G>A;c.5143C>G;c.5143C>T;c.5113C>T;c.5012G>A;c.5010delT;c.4999delC;c.4996C>T;c.4987A>T;c.4979C>T;c.4969C>T;c.4942C>T;c.4935G>A;c.4934G>A;c.4926delA;c.4922dupT;c.4918G>T;c.4899delT;c.4895delT;c.4895dupT;c.4864G>A;c.4858delC;c.4848delC;c.4841delA;c.4828G>T;c.4825delA;c.4825dupA;c.4814C>A;c.4805_4806delAA;c.4806delA;c.4798A>T;c.4794G>T;c.4770T>A;c.4767_4768insATAACCAA;c.4719_4729delTGCAAAGACTC;c.4720delG;c.4712_4715delAAAG;c.4694_4697delTTCT;c.4687delG;c.4686delA;c.4662_4663delGA;c.4658delA;c.4619delT;c.4561C>T;c.4542delT;c.4519delA;c.4512delG;c.4492_4496delGTTCT;c.4492_4493delGT;c.4492delG;c.4483delG;c.4483G>T;c.4474A>T;c.4473C>A;c.4473C>G;c.4460delA;c.4450delA;c.4446dupG;c.4430_4431delAG;c.4425_4426delAA;c.4423C>T;c.4408G>T;c.4382_4383delAC;c.4379delA;c.4363C>T;c.4345G>T;c.4339delG;c.4339dupG;c.4328_4331delAAGA;c.4318delT;c.4296_4300delTTCTC;c.4280delT;c.4272delC;c.4265_4266delAT;c.4242dupA;c.4241C>A;c.4201C>T;c.4199delC;c.4156C>T;c.4121_4124delTAGA;c.4103delC;c.4094_4100delATTTGAC;c.4072C>T;c.4045delA;c.4035delA;c.4006C>T;c.3994_3997delAGAG;c.3991_3992delAA;c.3984dupA;c.3982C>T;c.3967C>T;c.3964C>T;c.3922G>T;c.3913C>T;c.3907_3911delACCAA;c.3902delA;c.3870dupA;c.3863dupC;c.3860delT;c.3851_3852delCA;c.3842_3844delAGAinsGG;c.3844A>T;c.3833delA;c.3830delC;c.3827C>G;c.3772delT;c.3766G>T;c.3756delG;c.3735_3744delCCTTTTCTTAinsATTTCTTTTTCTTT;c.3736delC;c.3710delC;c.3692delC;c.3652delG;c.3637delA;c.3631A>T;c.3624delT;c.3607G>T;c.3565dupA;c.3548_3549delAA;c.3500dupA;c.3496A>T;c.3493G>T;c.3490delT;c.3421C>T;c.3416_3417delCT;c.3417dupT;c.3409_3410delCT;c.3388delA;c.3385delC;c.3371C>A;c.3344delT;c.3302_3303delAG;c.3300delA;c.3298A>T;c.3289C>T;c.3251C>G;c.3224delC;c.3203_3204delGA;c.3196C>T;c.3169G>A;c.3152delT;c.3150_3151insTC;c.3144G>A;c.3091_3094delAAGA;c.3053delA;c.3034G>C;c.3031A>T;c.2962_2963delAG;c.2945dupA;c.2412_2421delCTCCTCTAGT;c.2419dupA;c.2409delT;c.2404C>T;c.2397delT;c.2384_2388delGAACA;c.2383A>T;c.2373dupG;c.2360delA;c.2167G>A;c.2149C>T;c.2102_2106delTGGAA;c.2097G>A;c.2096T>A;c.2095A>C;c.2095A>G;c.2095A>T;c.2089_2090delGT;c.2090T>A;c.2066T>G;c.2058_2059delAC;c.2060T>C;c.2057C>G;c.2044G>T;c.2032A>T;c.2029T>C;c.2015_2017delTCT;c.2000delT;c.1996_1999delGACT;c.1996_1999dupGACT;c.1990_1991delCA;c.1991A>C;c.1988C>T;c.1985G>C;c.1965C>G;c.1958T>C;c.1957G>A;c.1952A>C;c.1947_1950delTTTG;c.1941_1944delAGTT;c.1934A>C;c.1913G>A;c.1912G>A;c.1904-1G>A;c.1904-37G>A;c.1892A>G;c.1834C>T;c.1814A>C;c.1812G>C;c.1808G>T;c.1804C>T;c.1754T>C;c.1752+5G>C;c.1750C>A;c.1748A>G;c.1736A>T;c.1730C>T;c.1729T>C;c.1726G>T;c.1703G>T;c.1688C>G;c.1682A>C;c.1682A>G;c.1681G>A;c.1675G>T;c.1667T>A;c.1661G>A;c.1660A>G;c.1653T>G;c.1649G>A;c.1648C>G;c.1648C>T;c.1640G>A;c.1639T>C;c.1636C>T;c.1630G>A;c.1619C>G;c.1618C>A;c.1596dupG;c.1596G>A;c.1595G>A;c.1594T>G;c.1585A>G;c.1560delT;c.1538-1G>T;c.1538-2A>T;c.1492G>A;c.1481T>C;c.1477A>G;c.1463C>G;c.1463C>T;c.1443+3A>C;c.1443+2T>C;c.1442_1443dupTG;c.1443+1G>A;c.1432G>A;c.1420G>T;c.1418A>G;c.1417T>C;c.1410_1413delTTTA;c.1406G>C;c.1400T>G;c.1397G>A;c.1394C>G;c.1390G>T;c.1357G>T;c.1350C>A;c.1348T>A;c.1348T>G;c.1338delA;c.1336dupC;c.1337G>A;c.1337G>C;c.1336C>T;c.1331_1332delAA;c.1331_1332delAAinsT;c.1331A>C;c.1331A>G;c.1325A>G;c.1324T>A;c.1324T>C;c.1316G>A;c.1311delG;c.1301G>A;c.1293delG;c.1293G>T;c.1234T>C;c.1226A>G;c.1214T>G;c.1207C>G;c.1203G>A;c.1200_1201delTT;c.1202G>A;c.1197_1198delAA;c.1189dupC;c.1175C>A;c.1175C>G;c.1172G>C;c.1165delC;c.1077_1080delTGAA;c.1078_1079delGA;c.1063C>T;c.1043G>C;c.1042T>C;c.1026T>A;c.985dupT;c.986G>A;c.986G>C;c.986G>T;c.984delT;c.985T>C;c.980T>C;c.974_975delTT;c.967G>A;c.948_951delAACA;c.943delG;c.941C>T;c.940A>G;c.935delT;c.935T>C;c.923C>T;c.919delA;c.920T>G;c.907delG;c.902G>A;c.902G>C;c.902G>T;c.899A>C;c.899A>T;c.896A>T;c.889delG;c.886C>T;c.883T>C;c.881C>T;c.872A>G;c.871G>T;c.854T>G;c.849delT;c.850G>A;c.850G>T;c.836T>A;c.832G>A;c.824A>G;c.822G>A;c.797G>A;c.796G>T;c.788-1G>A;c.788-1G>C;c.788-1G>T;c.788-2A>T;c.787+2T>C;c.787G>C;c.779C>G;c.775A>T;c.770_771insCC;c.764G>A;c.760A>T;c.755C>A;c.729delT;c.709C>T;c.695_698delAGAA;c.688_689delGA;c.685_686delTC;c.680G>A;c.676A>T;c.665A>T;c.592T>G;c.577G>A;c.571C>T;c.566C>A;c.566C>T;c.560T>A;c.557A>G;c.556G>A;c.554A>C;c.553A>G;c.545A>T;c.541G>A;c.535T>C;c.532C>G;c.525C>A;c.519_523delTACCT;c.514_515insTCAAGATA;c.515G>A;c.514T>C;c.493C>T;c.491G>T;c.489T>A;c.476T>C;c.472C>T;c.471G>A;c.446delC;c.440T>A;c.435_436insTTT;c.433G>C;c.430G>T;c.421G>T;c.415C>T;c.410C>T;c.407A>C;c.405T>A;c.404A>G;c.403G>A;c.398A>G;c.396A>C;c.388G>C;c.364_365delGT;c.350T>G;c.328A>G;c.323A>C;c.311T>A;c.296T>A;c.275G>T;c.270delG;c.266G>A;c.265+1G>T;c.265G>A;c.255_257delACC;c.250A>G;c.230T>C;c.224delA;c.225T>A;c.223G>T;c.217T>C;c.214G>A;c.209_212delTTGT;c.209T>C;c.201_202dupGA;c.203C>A;c.199_200delAA;c.201G>T;c.200A>C;c.199A>G;c.195C>A;c.185C>G;c.173delC;c.144-5C>G;c.144-11T>G;c.144-26A>T;c.143+1G>A;c.120delC;c.104A>G;c.98G>A;c.97T>G;c.89A>T;c.88G>A;c.86T>G;c.77T>C;c.77T>G;c.65G>C;c.43C>T;c.1A>G;IVS22 INV (Type 1/2)

Hemophilia B

Descripción enfermedad:
Hemophilia B follows an X-linked pattern of inheritance and is caused by pathogenic variants in the F9 gene located on chromosomal region Xq27.1-q27.2. The age of onset is neonatal/infantile. This disease is characterized by spontaneous or prolonged hemorrhages due to factor IX deficiency. The prevalence is 1/100,000 to 9/100,000.

c.82T>C;c.141T>A;c.148G>A;c.169C>T;c.218A>T;c.223C>T;c.224G>A;c.237A>C;c.253-1G>C;c.277+2T>C;c.278A>G;c.287A>C;c.301C>G;c.316G>A;c.328G>A;c.329A>G;c.479G>C;c.484C>T;c.496A>T;c.519dupA;c.540_541delAG;c.571C>T;c.572G>A;c.655C>T;c.676C>T;c.677G>A;c.682G>C;c.682G>T;c.697G>A;c.709C>T;c.755G>C;c.756T>G;c.835G>A;c.872A>T;c.880C>T;c.881G>A;c.892C>T;c.917A>G;c.998C>T;c.1025C>T;c.1031T>C;c.1058T>C;c.1064G>T;c.1069G>A;c.1070G>A;c.1088G>T;c.1120G>T;c.1135C>T;c.1136G>A;c.1144T>C;c.1150C>T;c.1151G>C;c.1151G>T;c.1180A>G;c.1187G>C;c.1189G>C;c.1217C>T;c.1228G>C;c.1231A>G;c.1232G>T;c.1240C>A;c.1307C>A;c.1307C>T;c.1324G>A;c.1328T>C;c.1357T>C;c.1369A>T

Tyrosinemia, type 1

Descripción enfermedad:
Tyrosinemia, type 1 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the FAH gene located on chromosomal region 15q25.1. The age of onset is variable. This disease is characterized by progressive liver disease, renal tubular dysfunction, porphyria-like crises and a dramatic improvement in prognosis following treatment with nitisinone. The birth incidence is 1/100,000, notably in Québec, Canada, and the prevalence is 1/100,000 to 1/120,000 newborns.

c.1A>G;c.47A>T;c.81+2T>C;c.82-1G>A;c.192G>T;c.192+1G>T;c.193-2A>G;c.314+1G>A;c.315-2A>G;c.401C>A;c.438delT;c.455G>A;c.456-2A>G;c.456G>A;c.492delC;c.520C>T;c.553+2_553+3delTG;c.554-1G>T;c.607-1G>A;c.615delT;c.698A>T;c.706+2T>G;c.707-1G>A;c.709C>T;c.744delG;c.780_781delTC;c.782C>T;c.786G>A;c.835delC;c.837+1G>A;c.939delC;c.960+1G>A;c.961-2A>C;c.963C>A;c.982C>T;c.1009G>A;c.1027G>T;c.1062+5G>A;c.1063-2A>G;c.1069G>T;c.1090G>T;c.1141A>G;c.1181-1G>A;c.1190delA

Raine syndrome

Descripción enfermedad:
Raine syndrome follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the FAM20C gene located on chromosomal region 7p22.3. The age of onset is neonatal/infantile. This disease is characterized by generalized osteosclerosis with periosteal bone formation, characteristic facial dysmorphism, brain abnormalities including intracerebral calcifications, and neonatal lethal course. The prevalence is below 1/1,000,000.

c.1093G>C;c.1136G>A;c.1163T>G;c.1225C>T;c.1364-2A>G;c.1446-1G>A

Fanconi anemia, complementation group A

Descripción enfermedad:
Fanconi anemia, complementation group A follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the FANCA gene located on chromosomal region 16q24.3. The age of onset is infantile. This disease is characterized by progressive pancytopenia with bone marrow failure, variable congenital malformations and predisposition to develop hematological or solid tumors. The prevalence is 1/1,000,000 to 9/1,000,000.

c.4261-2A>C;c.4260+2T>A;c.4260+1G>A;c.4257dupA;c.4130C>G;c.4124_4125delCA;c.4069_4082delGCTGTGGACATGTA;c.4015delC;c.4011-1G>A;c.3971C>T;c.3935-1G>T;c.3934+2T>C;c.3890dupA;c.3884T>A;c.3884T>G;c.3828+1G>A;c.3828+1G>C;c.3813dupA;c.3788_3790delTCT;c.3761_3762delAG;c.3761_3762dupAG;c.3763G>T;c.3745delC;c.3720_3724delAAACA;c.3696delT;c.3634dupT;c.3626+1G>T;c.3624C>T;c.3610_3613delCGGC;c.3592C>T;c.3558dupG;c.3408+1G>C;c.3391A>G;c.3382C>T;c.3349A>G;c.3348+1G>A;c.3188G>A;c.3085G>T;c.3066+1G>T;c.2990_2993delGTTA;c.2982-1G>C;c.2981+1G>A;c.2910delA;c.2870G>A;c.2853-2A>C;c.2852G>A;c.2851C>T;c.2839dupT;c.2840C>G;c.2778+2T>C;c.2763_2769delAGAGGAA;c.2749C>T;c.2730_2731delCT;c.2667delC;c.2630_2631delCA;c.2606A>C;c.2602-2A>T;c.2601+1G>T;c.2557C>T;c.2546delC;c.2535_2536delCT;c.2529C>A;c.2524delT;c.2398G>T;c.2303T>C;c.2222+1G>C;c.2175_2182delTTTCTGTC;c.2172dupG;c.2151+2T>C;c.2151+1G>A;c.2107C>T;c.2082_2088dupCAGCAGC;c.2026C>T;c.2015-1G>A;c.1981A>T;c.1944delG;c.1901-1G>A;c.1901-2A>G;c.1844dupC;c.1827-1G>A;c.1796_1800dupCCCGT;c.1777-1G>C;c.1776+1G>A;c.1771C>T;c.1734_1739delCTACGT;c.1715+1G>T;c.1615delG;c.1606delT;c.1567-1G>T;c.1489C>T;c.1476_1477delCA;c.1470+1G>A;c.1378C>T;c.1359+1G>C;c.1340C>G;c.1304G>A;c.1267C>T;c.1226-2A>G;c.1115_1118delTTGG;c.1074_1075delGT;c.1034_1035delAG;c.1006+1G>T;c.989_995delACAGCCC;c.916_917delAC;c.894-2A>G;c.863_866dupAGTC;c.862G>T;c.856C>T;c.827-1G>C;c.811C>T;c.793-1G>A;c.718C>T;c.710-1G>C;c.709+5G>A;c.709+2T>C;c.709+1G>C;c.643_644delTG;c.597-1G>C;c.596+2T>C;c.549G>A;c.523-1G>T;c.523-2A>G;c.522+1G>T;c.513G>A;c.427A>T;c.416_417delTG;c.401dupC;c.295C>T;c.283+1G>T;c.238delT;c.233_236delTTGA;c.190-1G>T;c.190-2A>T;c.189+1G>A;c.163C>T;c.154C>T;c.131dupA;c.100A>T;c.97delG;c.80-1G>T;c.79+1G>C;c.65G>A;c.11C>A;c.2T>A;c.2T>C;c.1A>C;c.1A>G;c.1A>T

Fanconi anemia, complementation group C

Descripción enfermedad:
Fanconi anemia, complementation group C follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the FANCC gene located on chromosomal region 9q22.3. The age of onset is infantile. This disease is characterized by progressive pancytopenia with bone marrow failure, variable congenital malformations and predisposition to develop hematological or solid tumors. The prevalence is 1/1,000,000 to 9/1,000,000.

c.1642C>T;c.1628C>A;c.1555dupA;c.1534-1G>T;c.1534-2A>G;c.1533+2T>C;c.1533+1G>C;c.1517G>A;c.1498G>T;c.1487T>G;c.1393C>T;c.1387_1388delTC;c.1333C>T;c.1329+1G>T;c.1309C>T;c.1302dupT;c.1290C>A;c.1182G>A;c.1162G>T;c.1155-1G>A;c.1151_1152delAT;c.1144delC;c.1103_1104delTG;c.1073-1G>C;c.1072+1G>A;c.1069C>T;c.1043_1044delTT;c.1037dupC;c.1015delA;c.996+1G>A;c.996+1G>T;c.946C>T;c.896+2T>G;c.896+1G>C;c.844-1G>C;c.843+1G>A;c.843+1G>C;c.831delA;c.808A>T;c.686+1G>T;c.640dupA;c.595delC;c.595dupC;c.553C>T;c.535C>T;c.521+1G>A;c.520C>T;c.487_490delGAGA;c.489_490delGA;c.457-1G>T;c.456+4A>T;c.455dupA;c.388G>T;c.368C>G;c.356_360delCTCAT;c.355_360delTCTCATinsA;c.346-1G>A;c.339G>A;c.319C>T;c.307C>T;c.251-2A>C;c.251-2A>G;c.165+1G>T;c.117delT;c.108_109dupTC;c.67delG;c.65G>A;c.37C>T;c.29dupG;c.-78-2A>G

Fanconi anemia, complementation group G

Descripción enfermedad:
Fanconi anemia, complementation group G follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the FANCG gene located on chromosomal region 9p13. The age of onset is infantile. This disease is characterized by progressive pancytopenia with bone marrow failure, variable congenital malformations and predisposition to develop hematological or solid tumors. The prevalence is 1/1,000,000 to 9/1,000,000.

c.1852_1853delAA;c.1795_1804delTGGATCCGTC;c.1747G>T;c.1642C>T;c.1480+1G>C;c.1077-2A>G;c.1066C>T;c.925-2A>G;c.907_908dupCT;c.778-1G>A;c.777+1G>A;c.652C>T;c.637_643delTACCGCC;c.510+1G>A;c.313G>T;c.307+1G>C;c.156dupG

Fumarase deficiency

Descripción enfermedad:
Fumarase deficiency follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the FH gene located on chromosomal region 1q42.1. The age of onset is neonatal/infantile. This disease is characterized by hypotonia, severe psychomotor impairment, convulsions, respiratory distress, feeding difficulties and frequent cerebral malformations, along with a distinctive facies, although some patients present with only moderate intellectual impairment. The prevalence is below 1,000,000.

c.1500G>A;c.1475_1476delTC;c.1469delG;c.1446_1449delAAAG;c.1430_1437dupAAAATGGA;c.1431_1433dupAAA;c.1394A>G;c.1391-1G>A;c.1391-1G>C;c.1391-2A>T;c.1390+2T>C;c.1390+1G>T;c.1370_1371insTCAC;c.1357_1358delCT;c.1349_1352delATGA;c.1349_1352dupATGA;c.1351G>T;c.1347delG;c.1339A>T;c.1302C>A;c.1293delA;c.1263delG;c.1255T>C;c.1250T>G;c.1236+1G>A;c.1236+1G>C;c.1209delT;c.1210G>T;c.1200delT;c.1189G>A;c.1157A>G;c.1139_1142delTGAC;c.1138dupA;c.1126C>T;c.1118A>G;c.1112delA;c.1108+1G>T;c.1097G>A;c.1093A>G;c.1083_1086delTGAA;c.1084G>C;c.1067T>A;c.1063G>T;c.1056dupT;c.1052C>A;c.1052C>G;c.1041delT;c.1027C>T;c.1021G>A;c.1020T>A;c.1007T>G;c.1000A>C;c.952C>T;c.944_945delTG;c.937G>T;c.935T>G;c.934T>C;c.923C>G;c.912_918delTTTTGTC;c.905-1G>A;c.905-1G>C;c.901dupA;c.879delT;c.820G>C;c.808delT;c.805delA;c.797dupT;c.793G>A;c.760C>T;c.757C>T;c.739G>T;c.739-2A>C;c.738+2T>C;c.737delA;c.736C>T;c.731T>G;c.706A>G;c.703C>T;c.698G>A;c.697C>T;c.689A>G;c.679C>T;c.671_672delAG;c.668_669delAA;c.634C>T;c.578_583delCAGCAA;c.584T>C;c.568_569delAC;c.566A>T;c.563delA;c.560C>A;c.560C>G;c.556_557delAG;c.557G>A;c.556-1G>C;c.556-2A>G;c.556-2A>T;c.555+1G>A;c.553_554insTG;c.554A>G;c.539A>G;c.524delT;c.521C>G;c.442C>T;c.439dupA;c.395_399delTAAAT;c.395delT;c.379-1G>A;c.379-2A>G;c.378+2T>C;c.349G>C;c.322C>T;c.320A>C;c.316delG;c.295_301delTTGAAGC;c.302G>C;c.301C>T;c.268-2A>G;c.267+1_267+10delGTAAGTGGCA;c.267+1G>A;c.267+1G>C;c.239dupA;c.204T>A;c.174_177dupTGAA;c.157G>T;c.139C>T;c.134delC;c.133-1G>A;c.40dupC;c.1A>G

Muscular dystrophy-dystroglycanopathy, type 5A, 5B and 5C

Descripción enfermedad:
Muscular dystrophy-dystroglycanopathy type 5 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the FKRP gene located on chromosomal region 19q13.32. The age of onset is neonatal or early infancy. There are three subtypes of dystroglycanopathies related to FKRP gene: subtype 5A, 5B and 5C. Subtype 5A is the most severe phenotype and is associated with congenital brain and eye anomalies, cobblestone lissencephaly, profound mental retardation, and death usually in the first years of life. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease. Subtype 5B represents an intermediate phenotype with or without congenital mental retardation, white matter changes and structural brain abnormalities. Finally, subtype 5C is the less severe phenotype characterized by limb-girdle muscular dystrophy, variable age at onset, normal cognition, and no structural brain changes.

c.1A>G;c.158_162dupTGCGG;c.160C>T;c.162_165dupGGAG;c.266C>T;c.387_390dupACCT;c.558dupC;c.764G>A;c.823C>T;c.826C>A;c.859_869delTTCGGCTGCAA;c.899T>C;c.919T>A;c.928G>T;c.941C>T;c.947C>G;c.1027G>T;c.1141delG;c.1141dupG;c.1154C>A;c.1170_1171delCG;c.1343C>T;c.1364C>A;c.1387A>G;c.1433T>C;c.1475delC;c.1486T>A

Muscular dystrophy-dystroglycanopathy, type 4A (Walker-Warburg syndrome); Type 4B; Type 4C (limb-girdle muscular dystrophy, type 13 [LGMD R13])

Descripción enfermedad:
Muscular dystrophy-dystroglycanopathy type 4 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the FKTN gene located on chromosomal region 9q31.2. The age of onset is neonatal or early infancy. There are three subtypes of dystroglycanopathies related to FKTN gene: subtype 4A, 4B and 4C. Subtype 4A is the most severe phenotype and is associated with congenital brain and eye anomalies, seizures, profound mental retardation, and death usually in the first years of life. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease. Subtype 4B represents an intermediate phenotype and congenital mental retardation is not a feature. Finally, subtype 4C is the less severe phenotype characterized by limb-girdle muscular dystrophy, onset in early childhood and cognition and brain structure are usually normal.

c.-1_2delAAT;c.42delG;c.106-2A>G;c.109G>T;c.139C>T;c.187_188delAT;c.330dupT;c.346C>T;c.369+1G>C;c.369+1G>T;c.370-2A>G;c.411C>A;c.429delA;c.454dupT;c.456_457delAC;c.509C>A;c.527T>C;c.607C>T;c.642dupT;c.658_661delCAGC;c.766C>T;c.770delC;c.780+1G>A;c.911-1G>A;c.919C>T;c.1106delT;c.1112A>G;c.1129_1130delAT;c.1167dupA;c.1172+1G>A;c.1173-2A>G;c.1173-1G>A;c.1173-1G>C;c.1363delG;c.1371_1381dupTATCCAGTTAT;c.1380dupA

Fragile X syndrome

Descripción enfermedad:
Fragile X syndrome follows an X-linked pattern of inheritance and is caused by pathogenic variants in the FMR1 gene located on chromosomal region Xq27.3. The symptoms are variable depending on the range of CGG triplet expansion. In complete mutation the onset is infantile in men and is characterized by intellectual disability, characteristic appearance (large head, long face, prominent forehead and chin, protruding ears) joint laxity and large testes after puberty. In carrier female, the symptoms are milder and include primary ovarian insufficiency. The prevalence is 1/2,500 (full mutation allele) to 1/4,000 (prevalence of symptomatic cases) for both genders.

Expanded allele_full mutation;Expanded allele_premutation

Fraser syndrome, type 1

Descripción enfermedad:
Fraser syndrome, type 1 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the gene FRAS1 located on chromosomal region 4q21.21. The age of onset is early infancy. Twenty-five per cent of affected infants are stillborn, while 20 % die before the age of 1 year. This disease is characterized mainly by cryptophthalmos and syndactyly, besides urinary and genital anormalities. The prevalence is <1:1,000,000.

c.370C>T;c.835_838delGTGT;c.1931delG;c.2719C>T;c.2722+1G>A;c.3010+1G>A;c.3370dupT;c.3799C>T;c.4271C>G;c.5125C>T;c.5605_5606insT;c.6433C>T;c.6963_6964dupGG;c.6991_6992insGG;c.7005delT;c.7522+1G>T;c.7551T>A;c.7813C>T;c.8098+2T>A;c.8403_8404delGT;c.8602C>T;c.9013C>T;c.10287delC;c.10948C>T;c.11160_11167delGCTGGAGA

Glycogen storage disease, type 1A

Descripción enfermedad:
Glycogen storage disease, type 1A follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the G6PC gene located on chromosomal region 17q21.31. The age of onset is infantile. This disease is characterized by poor tolerance to fasting, significant hepatomegaly and growth retardation. The incidence is 1/100,000.

c.79delC;c.79C>T;c.113A>T;c.150_151delGT;c.189G>A;c.229T>C;c.230+1G>C;c.231-1G>A;c.247C>T;c.248G>A;c.255C>A;c.258G>A;c.328G>A;c.370G>A;c.379_380dupTA;c.381C>A;c.447-1G>A;c.497T>G;c.499dupT;c.508C>T;c.516C>A;c.551G>T;c.474G>A;c.560C>G;c.562G>A;c.562G>C;c.648G>T;c.724C>T;c.809G>T;c.883C>T;c.969C>A;c.1039C>T

Dursun syndrome

Descripción enfermedad:
Dursun syndrome follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the G6PC3 gene located on chromosomal region 17q21.31. This disease is characterized by familial pulmonary arterial hypertension, cardiac abnormalities including atrial septal defect, leukopenia including intermittent neutropenia, lymphopenia, monocytosis, and anemia. The prevalence is 1:100,000.

c.130C>T;c.141C>G;c.210delC;c.346A>G;c.758G>A;c.778G>C;c.784G>C;c.829C>T;c.935dupT

Hemolytic anemia, G6PD deficient (favism)

Descripción enfermedad:
Hemolytic anemia, G6PD deficient (favism) is the most common genetic cause of chronic and drug-, food-, or infection-induced hemolytic anemia. G6PD catalyzes the first reaction in the pentose phosphate pathway, which is the only NADPH-generation process in mature red cells; therefore, defense against oxidative damage is dependent on G6PD. Most G6PD-deficient patients are asymptomatic throughout their life, but G6PD deficiency can be life-threatening. The most common clinical manifestations of G6PD deficiency are neonatal jaundice and acute hemolytic anemia, which in most patients is triggered by an exogenous agent, e.g., primaquine or fava beans. Acute hemolysis is characterized by fatigue, back pain, anemia, and jaundice. Increased unconjugated bilirubin, lactate dehydrogenase, and reticulocytosis are markers of the disorder. The striking similarity between the areas where G6PD deficiency is common and Plasmodium falciparum malaria (611162) is endemic provided evidence that G6PD deficiency confers resistance against malaria (Cappellini and Fiorelli, 2008).

c.1478G>A;c.1466G>T;c.1450C>T;c.1429G>A;c.1408C>T;c.1406G>C;c.1319G>A;c.1270G>C;c.1268G>A;c.1249C>T;c.1246A>G;c.1179C>A;c.1178A>T;c.1172C>T;c.1093G>A;c.1054T>C;c.961G>A;c.934G>C;c.896G>A;c.770G>T;c.727G>T;c.683G>C;c.653C>T;c.632A>T;c.583A>G;c.577G>A;c.473T>C;c.233T>C

Glycogen storage disease, type 2

Descripción enfermedad:
Glycogen storage disease, type 2 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the GAA gene located on chromosomal region 17q25.3. There are two forms: adult and infantile.The age of onset in this last form is before the age of three months. This disease is characterized by severe hypotonia, hypertrophic cardiomyopathy and progressive hepatomegaly. The incidence is 1/57,000 for the adult form and 1/138,000 for infantile form.

n.*1805T>G;c.-32-1G>C;c.1A>G;c.55delG;c.118C>T;c.169C>T;c.172C>T;c.236_246delCCACACAGTGC;c.241C>T;c.258delC;c.258dupC;c.281_282delCT;c.307T>G;c.343C>T;c.352C>T;c.365delT;c.379_380delTG;c.393delC;c.437delT;c.471delC;c.482_483delCC;c.525_526delTG;c.525delT;c.546+2_546+5delTGGG;c.546G>A;c.546G>C;c.569G>A;c.573C>A;c.655G>A;c.670C>T;c.692+2T>C;c.698delA;c.716delT;c.725C>T;c.736delC;c.768dupT;c.784G>A;c.853C>T;c.854C>G;c.858+2T>A;c.875A>G;c.877G>A;c.896T>C;c.896T>G;c.925G>A;c.934delC;c.989G>A;c.1004G>A;c.1051delG;c.1062C>A;c.1064T>C;c.1075G>T;c.1076-2A>G;c.1076-1G>A;c.1082C>T;c.1099delT;c.1115A>T;c.1124G>T;c.1128_1129delGGinsC;c.1129G>C;c.1134C>G;c.1143delC;c.1153delC;c.1156C>T;c.1165delG;c.1192dupC;c.1193delT;c.1194+2T>C;c.1195-1G>A;c.1222A>G;c.1292_1295dupTGCA;c.1309C>T;c.1316T>A;c.1326+1G>A;c.1326+2T>C;c.1327-2A>G;c.1411_1414delGAGA;c.1431delT;c.1437+1G>A;c.1438-2A>G;c.1438-1G>C;c.1441T>C;c.1447G>A;c.1465G>A;c.1478C>T;c.1496G>A;c.1548G>A;c.1551+1G>C;c.1551+1G>T;c.1552-3C>G;c.1552-2A>G;c.1556T>C;c.1561G>A;c.1564C>A;c.1564C>G;c.1567delT;c.1585_1586delTCinsGT;c.1634C>T;c.1650dupG;c.1655T>C;c.1687C>T;c.1754+1G>A;c.1799G>A;c.1802C>A;c.1802C>G;c.1802C>T;c.1824_1828dupATACG;c.1827delC;c.1827_1828insA;c.1832G>A;c.1843G>A;c.1847dupA;c.1856G>A;c.1912G>T;c.1927G>A;c.1933G>A;c.1933G>C;c.1933G>T;c.1935C>A;c.1941C>G;c.1942G>A;c.1961C>A;c.1979G>A;c.2012T>G;c.2014C>T;c.2015G>A;c.2040+1G>T;c.2041-1G>A;c.2061delC;c.2066_2070dupAGCCG;c.2104C>T;c.2105G>A;c.2105G>T;c.2136_2137delGT;c.2140delC;c.2161dupG;c.2173C>T;c.2185delC;c.2188G>T;c.2189+1G>T;c.2213G>A;c.2214G>A;c.2227C>T;c.2242delG;c.2242dupG;c.2237G>A;c.2237G>C;c.2238G>A;c.2238G>C;c.2242G>T;c.2269C>T;c.2281delGinsAT;c.2300delT;c.2331+2T>A;c.2332-1G>C;c.2367dupA;c.2407C>T;c.2495_2496delCA;c.2501_2502delCA;c.2512C>T;c.2544delC;c.2560C>T;c.2608C>T;c.2646+2T>A;c.2647-1_2648delGAA;c.2662G>T;c.2704_2716dupCAGAAGGTGACTG;c.2704C>T;c.2706delG;c.2815_2816delGT

Krabbe disease

Descripción enfermedad:
Krabbe disease follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the GALC gene located on chromosomal region 14q31.3. There are two forms of the disease: infantile form (2-6 months onset) more severe and adult form less severe. It is a degenerative disorder that affects the nervous system characterized by a muscle stiffness, blindness, deafness, and eventually death. The incidence is 1/100,000-1/250,000 and the prevalence is 1/100,000.

c.2056T>C;c.1987T>G;c.1964delC;c.1912-1G>C;c.1911+1_1911+5delGTAAG;c.1901delT;c.1896_1900delCACGT;c.1901T>C;c.1890T>A;c.1884dupA;c.1851delT;c.1837G>T;c.1835-1G>A;c.1814dupA;c.1796T>G;c.1723_1724insT;c.1712dupC;c.1700A>C;c.1695delT;c.1670+1G>A;c.1665C>G;c.1592G>A;c.1591C>T;c.1586C>T;c.1543G>A;c.1541T>C;c.1488_1489+2delTGGT;c.1489+1_1489+2delGT;c.1488_1489delTG;c.1472delA;c.1468T>A;c.1426dupA;c.1399dupA;c.1338+1G>C;c.1273delG;c.1272_1273insTAG;c.1186C>T;c.1161+2T>G;c.1153G>T;c.1075_1084delAAGACAGTTG;c.1065G>A;c.1031C>G;c.1021delG;c.1012delG;c.972delG;c.955delT;c.953C>G;c.952C>G;c.946C>T;c.908+1G>A;c.908+1G>T;c.908C>T;c.857G>A;c.850G>A;c.827_828delTT;c.749T>C;c.658C>T;c.655C>T;c.628A>T;c.621+1G>A;c.599C>A;c.583-1G>C;c.582+1G>A;c.533G>A;c.521delA;c.489G>A;c.467_468dupGG;c.453G>A;c.442+2T>G;c.433dupA;c.430delA;c.415A>T;c.388G>A;c.387C>G;c.379C>T;c.331G>A;c.328+1G>T;c.243_244dupGA;c.205C>T;c.196G>A;c.195+1G>A;c.195+1G>C;c.195G>C;c.169G>A

Galactokinase deficiency with cataracts

Descripción enfermedad:
Galactokinase deficiency is an autosomal recessive disorder that causes cataract formation in children not maintained on a lactose-free diet. Cataract formation is the result of osmotic phenomena caused by the accumulation of galactitol in the lens (Asada et al., 1999).

c.1144C>T;c.944+1G>T;c.612-1G>A;c.410delG;c.238G>T;c.82C>A

Mucopolysaccharidosis, type 4A

Descripción enfermedad:
Mucopolysaccharidosis, type 4A is an autosomal recessive lysosomal storage disease characterized by intracellular accumulation of keratan sulfate and chondroitin-6-sulfate. Key clinical features include short stature, skeletal dysplasia, dental anomalies, and corneal clouding. Intelligence is normal and there is no direct central nervous system (CNS) involvement, although the skeletal changes may result in neurologic complications. There is variable severity, but patients with the severe phenotype usually do not survive past the second or third decade of life (Montano et al., 2008).McKusick (1972) noted that between 1929 and 1959, a miscellany of skeletal disorders was included in the Morquio category, including various types of spondyloepiphyseal dysplasia (183900) and multiple epiphyseal dysplasia (132400). Nelson et al. (1988) proposed the division of MPS IVA into 3 subgroups: severe classic, intermediate, and mild, reflecting clinical variability observed in 12 enzymatically proven cases. Those who were only mildly affected showed a relatively high residual enzyme activity.

c.1577G>A;c.1503C>G;c.1478A>G;c.1435C>T;c.1193C>T;c.1189A>G;c.1174C>T;c.1037G>A;c.953C>G;c.919G>T;c.916+1G>A;c.916+1G>C;c.889G>A;c.889G>T;c.878C>T;c.868T>G;c.794G>A;c.758G>A;c.722C>A;c.707G>A;c.630C>G;c.629A>G;c.560A>G;c.503C>T;c.495G>A;c.481G>A;c.469C>A;c.439T>A;c.433G>A;c.431T>C;c.355A>T;c.349C>T;c.298C>G;c.223T>G;c.196G>A;c.157G>A;c.140T>A;c.139-2A>G

Galactosemia

Descripción enfermedad:
Galactosemia follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the GALT gene located on chromosomal region 9p13.3. The age of onset is neonatal. This disease is characterized by feeding difficulties, lethargy, and severe liver disease. Long-term complications appear including cognitive impairments, motor deficits, and ovarian dysfunction with reduced fertility in women and diminished bone density. The prevalence is 1/40,000-1/60,000.

c.1A>G;c.18delC;c.25C>T;c.41delCinsTT;c.71_72insA;c.82G>C;c.82G>T;c.83-2A>G;c.90G>C;c.95T>A;c.98G>A;c.113A>C;c.118G>T;c.130G>A;c.130G>T;c.132delG;c.136_140delGCTCA;c.152G>A;c.152G>T;c.158G>A;c.160C>T;c.163G>T;c.180delG;c.197C>A;c.199C>T;c.203A>C;c.207_214delCCCTCTCA;c.220_221delCT;c.220_221insG;c.221T>C;c.238C>T;c.253-2A>G;c.265T>C;c.265T>G;c.285T>G;c.289_291delAAC;c.289A>G;c.290A>G;c.292G>A;c.299C>G;c.307C>T;c.308A>G;c.328+2T>C;c.329-2A>C;c.334dupA;c.337G>A;c.341A>T;c.350T>C;c.354A>C;c.367C>T;c.368G>A;c.374T>C;c.377+1G>T;c.378-2A>T;c.385A>T;c.386T>C;c.392T>G;c.398_399dupCC;c.396C>A;c.400delT;c.404C>G;c.404C>T;c.410dupT;c.413C>T;c.416T>C;c.424A>G;c.425T>A;c.425T>C;c.428C>T;c.442C>G;c.442C>T;c.445dupG;c.443G>A;c.448G>C;c.460T>C;c.460T>G;c.462G>A;c.482T>C;c.490C>T;c.499T>C;c.502_504delGTG;c.502G>A;c.502G>T;c.505C>A;c.507+2T>C;c.508-1G>C;c.509T>A;c.509T>C;c.513delT;c.512T>C;c.524G>A;c.528_529insG;c.536G>A;c.539G>T;c.541T>G;c.542C>T;c.547C>A;c.550C>G;c.552C>A;c.553C>T;c.554C>A;c.556C>A;c.556C>T;c.558C>A;c.562C>T;c.563A>G;c.564+1G>A;c.564+1G>T;c.565_578delGTATGGGCCAGCAG;c.565-2A>G;c.568T>C;c.574A>G;c.575G>A;c.580T>C;c.584T>C;c.594T>G;c.595G>A;c.598delC;c.601C>T;c.602G>A;c.607G>A;c.610C>T;c.611G>C;c.616C>T;c.619C>T;c.626A>C;c.626A>G;c.627T>A;c.634C>T;c.635A>C;c.650T>C;c.652delC;c.658dupG;c.658G>A;c.667C>A;c.670delC;c.677T>C;c.680T>C;c.687G>T;c.687+1G>T;c.687+2T>C;c.688-2A>C;c.691C>T;c.692G>A;c.697G>C;c.719_728delTAGTACTGGT;c.745T>C;c.747G>A;c.748C>A;c.756G>T;c.761dupT;c.770C>T;c.772C>T;c.779_790delATGTGCGGCGGC;c.775C>T;c.776G>A;c.785G>C;c.790delC;c.790_792delCTAinsTAG;c.812A>G;c.814C>G;c.814C>T;c.815G>A;c.820+13A>G;c.821-2A>G;c.824delT;c.833T>A;c.844C>G;c.854A>G;c.855G>T;c.865C>T;c.866T>G;c.871G>A;c.872A>T;c.882delT;c.881T>A;c.888C>G;c.899G>A;c.904+1G>T;c.905-2A>G;c.905-1G>A;c.912dupC;c.920C>A;c.922G>A;c.938G>A;c.939G>A;c.947G>A;c.948G>A;c.949delC;c.950A>G;c.951G>T;c.952delC;c.957C>A;c.959C>T;c.967T>C;c.967T>G;c.968A>G;c.974C>T;c.976delC;c.979delC;c.980T>C;c.982C>T;c.983G>A;c.985T>C;c.986C>T;c.989C>T;c.997C>G;c.997C>T;c.998G>A;c.998G>T;c.1001A>G;c.1006A>T;c.1018G>A;c.1018G>T;c.1024C>A;c.1030C>A;c.1034C>A;c.1047delC;c.1048delA;c.1048A>G;c.1052delC;c.1057C>T;c.1059+1G>T;c.1060-1G>A;c.1098C>A;c.1108C>T;c.1138T>C;c.1140A>C

Cerebral creatine deficiency syndrome type 2

Descripción enfermedad:
Cerebral creatine deficiency syndrome type 2 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the GAMT gene located on chromosomal region 19p13.3. The age of onset is infantile. This disease is characterized by intellectual disability, seizures and behavioral problems, often in conjunction with pyramidal and/or extrapyramidal manifestations with muscular hypotony. Biochemical symptoms are also included with high urinary excretion of guanidinoacetate, low urinary excretion of creatinine and creatine depletion in brain and muscles.

c.522G>A;c.506G>A;c.503A>C;c.491dupG;c.491G>A;c.419C>A;c.410A>C;c.328G>T;c.327G>A;c.316C>T;c.299_311dupGGGACTGGGCCCC;c.148A>C;c.133T>A;c.59G>C

Gaucher disease

Descripción enfermedad:
Gaucher disease follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the GBA gene located on chromosomal region 1q22. Gaucher disease encompasses a continuum of clinical findings from a perinatal lethal disorder to an asymptomatic type. There are three major clinical types (1, 2, and 3) and two other subtypes (perinatal-lethal and cardiovascular). Type 1 is characterized by the presence of clinical or radiographic evidence of bone disease, hepatosplenomegaly, anemia and thrombocytopenia, lung disease, and the absence of primary central nervous system disease. GD types 2 and 3 are characterized by the presence of primary neurologic disease. Type 2 has an onset before age two years, limited psychomotor development, and a rapidly progressive course with death by age two to four years. Type 3 may have onset before age two years, but often have a more slowly progressive course, with survival into the third or fourth decade. The perinatal-lethal form is associated with ichthyosiform or collodion skin abnormalities or with nonimmune hydrops fetalis. The cardiovascular form is characterized by calcification of the aortic and mitral valves, mild splenomegaly, corneal opacities, and supranuclear ophthalmoplegia. Cardiopulmonary complications have been described with all the clinical subtypes, although varying in frequency and severity. The incidence is 1/60,000 and the prevalence is approximately 1/100,000.

c.1604G>A;c.1603C>T;c.1549G>A;c.1504C>T;c.1448T>C;c.1448T>G;c.1397T>G;c.1361C>G;c.1348T>A;c.1343A>T;c.1342G>C;c.1319C>T;c.1312G>A;c.1309G>T;c.1307T>C;c.1301G>C;c.1297G>T;c.1295G>T;c.1279G>T;c.1274dupA;c.1246G>A;c.1240G>C;c.1240G>T;c.1228C>G;c.1226A>G;c.1208G>C;c.1192C>T;c.1184C>T;c.1174C>G;c.1171G>C;c.1141T>G;c.1098dupA;c.1090G>A;c.1085C>T;c.1060G>C;c.1053G>T;c.1049A>G;c.1043C>T;c.1029delT;c.983C>T;c.914delC;c.896T>C;c.887G>A;c.886C>T;c.870C>A;c.866G>C;c.764T>A;c.763T>G;c.754T>A;c.751T>C;c.721G>A;c.703T>C;c.701G>A;c.680_681delATinsGG;c.681T>G;c.680A>G;c.667T>C;c.630delC;c.625C>T;c.586A>C;c.580A>T;c.533delC;c.509G>T;c.508C>T;c.487delG;c.481C>T;c.476G>A;c.475C>T;c.431T>G;c.407C>A;c.354G>C;c.259C>T;c.254G>A;c.160G>T;c.115+1G>A;c.93_94insG;c.84dupG;c.73delC

Glycogen storage disease, type 4

Descripción enfermedad:
Glycogen storage disease, type 4 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the GBE1 gene located on chromosomal region 3p12.2. The age of onset is infantile. This disease is characterized by failure to thrive; hepatomegaly, liver dysfunction, and progressive liver cirrhosis; hypotonia; cardiomyopathy and, finally, death.

c.2052+1G>A;c.1909C>T;c.1883A>G;c.1774G>T;c.1643G>A;c.1634A>G;c.1604A>G;c.1571G>A;c.1570C>T;c.1544G>A;c.1543C>T;c.1468delC;c.1345G>T;c.1239delT;c.1064G>A;c.993-1G>T;c.986A>C;c.986A>G;c.784C>T;c.783-1G>A;c.771T>A;c.760A>G;c.691+2T>C;c.671T>C;c.466_470delCGTAT;c.415G>T;c.288delA;c.143+1G>A

Glutaricaciduria, type 1

Descripción enfermedad:
Glutaricaciduria, type 1 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the GCDH gene located on chromosomal region 19p13.2. The age of onset is infantile or neonatal. This disease is characterized by encephalopathic crises resulting in striatal injury and a severe dystonic dyskinetic movement disorder. The prevalence is 1 in 100,000 births.

c.74C>A;c.79delG;c.80_81delCG;c.172G>T;c.198delC;c.219delC;c.226C>T;c.262C>T;c.271+1G>A;c.272-2A>C;c.281G>T;c.334G>T;c.339T>G;c.356C>T;c.382C>T;c.383G>A;c.395G>A;c.416C>T;c.431A>C;c.456C>G;c.482G>A;c.514G>T;c.532G>A;c.533G>A;c.541G>C;c.542A>G;c.572T>C;c.636-4_639delCCAGGATC;c.636-3_639delCAGGATC;c.636-1G>A;c.646_649dupTCGC;c.665_668delTTGT;c.675G>A;c.680G>C;c.731delG;c.743C>T;c.751C>T;c.764C>T;c.769C>T;c.770G>A;c.795_796insCTATGATCATC;c.848delT;c.853-2A>G;c.873delC;c.877G>A;c.881G>C;c.883T>C;c.892G>A;c.914C>T;c.937C>T;c.997C>T;c.1002_1003delGA;c.1031C>T;c.1054C>T;c.1060G>A;c.1063C>T;c.1082+1G>T;c.1093G>A;c.1147C>T;c.1156C>G;c.1156C>T;c.1173delG;c.1173dupG;c.1168G>C;c.1169G>C;c.1198G>A;c.1199dupT;c.1204C>T;c.1205G>A;c.1213A>G;c.1239C>A;c.1239C>G;c.1240G>A;c.1244-2A>C;c.1244-2A>G;c.1247C>T;c.1262C>T;c.1317A>G

Hyperphenylalaninemia, BH4-deficient, type B

Descripción enfermedad:
Hyperphenylalaninemia, BH4-deficient, type B is a disease characterized by malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency, and defective neurotransmission due to depletion of the neurotransmitters dopamine and serotonin. The principal symptoms include: psychomotor retardation, tonicity disorders, convulsions, drowsiness, irritability, abnormal movements, hyperthermia, hypersalivation, and difficulty swallowing. Some patients may present a phenotype of intermediate severity between severe hyperphenylalaninemia and mild dystonia. In this intermediate phenotype, there is marked motor delay, but no mental retardation and only minimal, if any, hyperphenylalaninemia.

c.662T>C;c.631_632delAT;c.633G>A;c.626+1G>A;c.626+1G>T;c.614T>A;c.610delG;c.607G>A;c.602G>A;c.595C>G;c.586G>T;c.551G>A;c.541+1G>C;c.541+1G>T;c.510-1G>A;c.510-1G>C;c.431A>C;c.404T>A;c.401A>T;c.344-1G>A;c.344-1G>C;c.343G>A;c.323G>A;c.262C>T;c.142C>T;c.3G>C;c.1A>T

Combined oxidative phosphorylation deficiency, type 1

Descripción enfermedad:
Combined oxidative phosphorylation deficiency, type 1 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the GFM1 gene located on chromosomal region 3q25.32. The age of onset is from early infancy until adult. This disease is characterized by ptosis, external ophthalmoplegia, proximal myopathy and exercise intolerance, cardiomyopathy, sensorineural deafness, optic atrophy, pigmentary retinopathy, and diabetes mellitus.

c.139C>T;c.273delC;c.521A>G;c.688G>A;c.757C>T;c.805C>T;c.1354_1357delGACA;c.1544T>G;c.1589_1590delAG;c.1653delT;c.2068C>T

Deafness, autosomal recessive, type 1A

Descripción enfermedad:
Autosomal recessive nonsyndromic sensorineural deafness type 1A follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the GJB2 gene located on chromosomal region 13q12.11. The age of onset is infantile. This disease is characterized by congenital, non-progressive, mild-to-profound sensorineural hearing impairment. No other associated medical findings are present.

c.647_650delGATA;c.645delT;c.632_633delGT;c.617A>G;c.605G>T;c.592_600delGTGTCTGGAinsCAGTGTTCATGACATTC;c.598G>A;c.598G>T;c.596C>T;c.575_576delCA;c.564_565delGA;c.551G>A;c.551G>C;c.550C>T;c.535G>A;c.516G>A;c.508_511dupAACG;c.506G>A;c.465T>A;c.456C>A;c.439G>A;c.428G>A;c.427C>T;c.416G>A;c.408C>A;c.402delG;c.400T>C;c.389G>C;c.385G>T;c.379C>T;c.370C>T;c.365A>T;c.358_360delGAG;c.334_335delAA;c.327_328delGGinsA;c.313_326delAAGTTCATCAAGGG;c.310_323delAGGAAGTTCATCAA;c.299_300delAT;c.299A>T;c.298C>T;c.290dupA;c.280_284dupCACGT;c.283G>A;c.279G>A;c.270dupA;c.269dupT;c.269T>C;c.250G>A;c.250G>C;c.250G>T;c.246C>G;c.239A>C;c.238C>T;c.235delC;c.232dupG;c.231G>A;c.230G>A;c.229T>C;c.224G>A;c.223C>G;c.223C>T;c.218A>G;c.196G>C;c.196G>T;c.194A>G;c.193T>C;c.176G>A;c.176G>C;c.175G>A;c.175G>C;c.172C>G;c.172C>T;c.169C>T;c.167delT;c.164C>A;c.162C>A;c.158G>A;c.148G>A;c.148G>T;c.139G>T;c.136G>A;c.134G>A;c.132G>A;c.132G>C;c.131G>A;c.131G>C;c.125_127delAGG;c.119C>A;c.119C>G;c.109G>T;c.101T>G;c.95G>A;c.95G>T;c.94C>A;c.94C>T;c.71G>A;c.66G>T;c.51_62delCACCAGCATTGGinsA;c.59T>C;c.50C>T;c.44A>C;c.35delG;c.35dupG;c.35G>T;c.34G>C;c.34G>T;c.19C>T;c.11delG;c.9G>A;c.1A>G;c.-23+1G>A;c.-23G>T

Fabry disease

Descripción enfermedad:
Fabry disease is an X-linked inborn error of glycosphingolipid catabolism resulting from deficient or absent activity of the lysosomal enzyme alpha-galactosidase A. This enzymatic defect leads to the systemic accumulation of globotriaoslyceramide (Gb3) and related glycosphingolipids in the plasma and cellular lysosomes of vessels, nerves, tissues, and organs throughout the body (Nance et al., 2006). The disorder is a systemic disease, manifest as progressive renal failure, cardiac disease, cerebrovascular disease, small-fiber peripheral neuropathy, and skin lesions, among other abnormalities (Schiffmann, 2009).An atypical variant of Fabry disease has been reported in which cardiac disease, specifically left ventricular hypertrophy, with or without renal failure, develops in the sixth decade of life. These patients have residual GLA activity (Nakao et al., 1995; Nakao et al., 2003). Although Fabry disease was previously considered to be an X-linked recessive disorder, Wang et al. (2007) found that heterozygous women with Fabry disease experience significant life-threatening conditions requiring medical treatment and intervention. Thus, heterozygous Fabry women should not be called carriers, as this term underestimates the seriousness of the disease in these patients. Clarke (2007) and Schiffmann (2009) provided detailed reviews of Fabry disease.

c.1246C>T;c.1241T>C;c.1235_1236delCT;c.1229C>T;c.1228A>G;c.1225C>G;c.1225C>T;c.1192G>T;c.1188delC;c.1157A>C;c.1124G>C;c.1118G>A;c.1117G>A;c.1095T>A;c.1088G>A;c.1081G>A;c.1081G>C;c.1077delT;c.1072_1074delGAG;c.1072G>A;c.1069C>T;c.1067G>C;c.1066C>T;c.1057_1058delAT;c.1055_1056delCT;c.1037delG;c.1033_1034delTC;c.1025G>A;c.1024C>G;c.1024C>T;c.1023A>C;c.1021G>T;c.1020G>A;c.1018T>C;c.999+2T>C;c.996_999delACAG;c.983G>C;c.982G>A;c.982G>C;c.980A>G;c.980A>T;c.979C>A;c.979C>T;c.974G>A;c.973G>A;c.966C>A;c.959_962delATCA;c.950T>G;c.916C>T;c.902G>A;c.901C>T;c.899T>C;c.896A>G;c.893A>G;c.890C>T;c.888G>A;c.887T>C;c.886A>G;c.879_880delTTinsAATC;c.865A>T;c.861G>A;c.861G>T;c.847C>T;c.842_844delTAA;c.835C>G;c.830G>A;c.826A>G;c.823delC;c.823C>T;c.815A>G;c.806T>C;c.806T>G;c.802-3_802-2delCA;c.802-2A>G;c.802-2A>T;c.801G>A;c.797A>T;c.791A>T;c.790G>T;c.785G>A;c.784T>C;c.777delA;c.776C>G;c.761T>C;c.748C>T;c.735G>A;c.734G>A;c.730G>A;c.730G>C;c.718_719delAA;c.713G>A;c.707G>A;c.704C>G;c.680G>A;c.680G>C;c.679C>T;c.677G>A;c.670A>G;c.667T>C;c.666C>A;c.662_663delAG;c.661C>T;c.658C>T;c.657C>G;c.647A>G;c.644A>G;c.641C>T;c.640-1G>A;c.640-1G>T;c.640-801G>A;c.638A>G;c.630delC;c.622_623delAT;c.613_621delCCTCTTTAT;c.620A>C;c.620A>G;c.614C>T;c.613C>A;c.610T>C;c.607G>A;c.606T>G;c.605G>A;c.561G>A;c.548G>A;c.548G>T;c.548-1G>A;c.548-2A>G;c.540G>T;c.509A>G;c.485G>A;c.484T>C;c.469C>T;c.466G>A;c.456C>A;c.443G>A;c.439G>A;c.436C>T;c.427G>A;c.427G>C;c.424T>C;c.422C>T;c.394G>A;c.386T>C;c.370-2A>G;c.369+2T>G;c.369+1G>A;c.361_364delGCTA;c.337T>A;c.335G>A;c.335G>T;c.334C>T;c.295dupC;c.290C>T;c.285G>A;c.281G>A;c.274G>A;c.274G>T;c.272T>A;c.272T>C;c.256T>C;c.254G>A;c.244A>T;c.242G>A;c.235G>T;c.195-1G>C;c.195-1G>T;c.166T>G;c.154T>C;c.146G>C;c.137A>G;c.137A>T;c.131G>A;c.127G>A;c.125T>C;c.124A>G;c.119C>G;c.118C>T;c.107T>G;c.104G>A;c.101A>G;c.98A>G;c.95T>C;c.80delC;c.59_72dupCCCTCGTTTCCTGG;c.59C>A;c.58G>C;c.26delA;c.19G>T;c.2T>C

GM1-gangliosidosis, types 1-3; Mucopolysaccharidosis, type 4B (Morquio)

Descripción enfermedad:
Gangliosidosis GM1, type 1 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the GLB1 gene located on chromosomal region 3p22.3. Although the three types differ in severity, their features can overlap significantly. The age of onset in type 1 is infantile, in type 2 is late-infantile or juvenile and adult in type 3. This disease is characterized by arrest/regression of neurological development, hypotonia, visceromegaly, macular cherry-red spots, dysostosis and coarse facial features. The prevalence is 1:100,000 a 200,000 newborn.

c.1915T>A;c.1912C>T;c.1890G>A;c.1877A>G;c.1790C>T;c.1778dupA;c.1721dupG;c.1693G>T;c.1671G>T;c.1654_1655insGA;c.1644_1647delTCTC;c.1642A>G;c.1624-2A>G;c.1623+1G>A;c.1600_1610dupGGTGCATATAT;c.1589G>A;c.1514G>A;c.1513C>T;c.1499dupA;c.1487A>T;c.1469G>A;c.1465G>A;c.1457G>A;c.1377+1G>A;c.1332dupG;c.1318_1319delCT;c.1288-2A>G;c.1221delA;c.1212+1G>T;c.1195C>T;c.1148C>T;c.1091A>G;c.1066T>C;c.1045G>A;c.990delC;c.985C>T;c.962G>T;c.952T>G;c.877+1G>A;c.838dupG;c.789_792delGGTT;c.770delA;c.766C>T;c.746G>A;c.745C>T;c.735dupT;c.696+2T>C;c.667C>T;c.625T>G;c.608T>G;c.601+2T>C;c.587G>A;c.586C>A;c.586C>T;c.582_584delTCT;c.569_570delAA;c.541-1G>A;c.540+2T>C;c.511G>A;c.420G>A;c.391T>C;c.389+1G>A;c.389+1G>C;c.389C>T;c.346C>T;c.320G>A;c.319C>T;c.315C>G;c.313delT;c.296T>C;c.289C>T;c.75+1G>C

Glycine encephalopathy

Descripción enfermedad:
Glycine encephalopathy follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in GLDC gene located on chromosomal region 9p24.1. The age of onset is neonatal/infantile. This disease is characterized by lethargy or even coma, hypotonia, hiccups, myoclonic jerks, and breathing/swallowing disorders, with subsequent intellectual deficit, spasticity and intractable seizures. The prevalence is 1:1,000,000-9:1,000,000.

c.2938A>G;c.2919+1G>A;c.2891dupA;c.2839-1G>C;c.2838+2T>C;c.2666-1G>A;c.2665+1G>C;c.2656C>T;c.2614A>T;c.2584G>A;c.2574T>G;c.2527C>T;c.2481_2484delACAA;c.2474G>A;c.2458-1G>T;c.2458-2A>G;c.2423_2426dupGTTC;c.2422delA;c.2414G>A;c.2405C>T;c.2317A>T;c.2316-1G>A;c.2315+2T>A;c.2311G>A;c.2306C>T;c.2293C>T;c.2284G>A;c.2281G>A;c.2281G>C;c.2258A>C;c.2216G>A;c.2213_2214delGT;c.2203-2A>G;c.2186delC;c.2182G>C;c.2177T>A;c.2153_2155delATCinsTCCTGGTTTA;c.2098C>G;c.2081_2088delCTATCATG;c.2080G>C;c.1996C>T;c.1926+1G>A;c.1888C>T;c.1868_1869dupAT;c.1850+1G>T;c.1822_1832delTATGACCAGGT;c.1832T>G;c.1786C>T;c.1742C>G;c.1723G>T;c.1705G>A;c.1691G>T;c.1654A>G;c.1595C>G;c.1580+2T>G;c.1545G>C;c.1444dupG;c.1402-1G>C;c.1401+1G>A;c.1382G>A;c.1342G>T;c.1285_1286insCAAA;c.1270C>T;c.1194C>A;c.1175delC;c.1166C>T;c.1111C>G;c.1108C>T;c.1054delA;c.1009C>T;c.1002dupT;c.985C>A;c.937G>C;c.887T>G;c.861+1G>T;c.847G>C;c.808G>T;c.806C>T;c.793delC;c.706C>T;c.605C>T;c.499G>T;c.482A>G;c.457G>T;c.449A>C;c.335-1G>C;c.334+1G>C;c.334+1G>T;c.322G>T;c.255+1G>A;c.245T>G;c.128delA;c.28delC;c.2T>C

Lethal congenital contracture syndrome, type 1; Congenital arthrogryposis with anterior horn cell disease

Descripción enfermedad:
Lethal congenital contracture syndrome, type 1 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the GLE1 gene located on chromosomal region 9q34.11. The age of onset is neonatal. This disease is characterized by total fetal akinesia (detectable since the 13th week of gestation) accompanied by hydrops, micrognathia, pulmonary hypoplasia, pterygia and multiple joint contractures (usually flexion contractures in the elbows and extension in the knees), leading invariably to death before the 32nd week of gestation. Lack of anterior horn motoneurons, severe atrophy of the ventral spinal cord and severe skeletal muscle hypoplasia are characteristic neuropathological findings, with no evidence of other organ structural anomalies. Mutation in the GLE1 gene can also cause congenital arthrogryposis with anterior horn cell disease (CAAHD). CAAHD is an autosomal recessive neuromuscular disorder with highly variable severity. Affected individuals are usually noted to have contractures in utero on prenatal ultrasound studies, and present at birth with generalized contractures manifest as arthrogryposis multiplex congenita (AMC). Patients have severe hypotonia with respiratory insufficiency, often resulting in death in infancy or early childhood. Some patients may survive into later childhood with supportive care, but may be unable to walk or sit independently due to a combination of muscle weakness and contractures. Cognition may be normal. The disorder also includes multiple congenital anomalies associated with AMC and hypotonia, including high-arched palate, myopathic facies, and bulbar weakness. Neuropathologic studies demonstrate severe loss of anterior horn cells in the spinal cord, as well as diffuse motor neuron axonopathy (summary by Smith et al., 2017 and Tan et al., 2017).

c.898-2A>G;c.1412_1413delAG;c.2051T>C;c.2069_2072delTTCT

Inclusion body myopathy, type 2 (Nonaka myopathy)

Descripción enfermedad:
Inclusion body myopathy, type 2 (Nonaka myopathy) follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the GNE gene located on chromosomal region 9p13.3. The age of onset is adult. This disease is characterized by progressive muscle weakness and joint deformity. The prevalence is 1:500-1:1,000.

c.2228T>C;c.2179G>A;c.2008C>T;c.1985C>T;c.1984G>A;c.1937C>G;c.1891G>A;c.1874delT;c.1853T>C;c.1833delC;c.1820G>A;c.1807G>C;c.1779delC;c.1702_1709delTTTGTTAC;c.1664C>T;c.1649A>G;c.1636_1637delGA;c.1578G>A;c.1510delT;c.1399C>T;c.1376delG;c.1355T>C;c.1351C>T;c.1251delA;c.1225G>T;c.1163+2dupT;c.1009C>T;c.1002T>A;c.986T>C;c.949C>T;c.922C>T;c.890G>A;c.889C>T;c.881G>T;c.880C>T;c.830G>A;c.829C>T;c.815T>G;c.748C>T;c.740T>C;c.729dupA;c.710-2A>G;c.709+1delG;c.705G>A;c.694_697dupATTC;c.665C>G;c.620A>T;c.604A>G;c.577C>T;c.563_564delAT;c.528_531delTATC;c.479G>A;c.478C>T;c.268C>T;c.257+1G>A;c.115C>T;c.97G>T

Mucolipidosis 2 alpha/beta; Mucolipidosis 3 alpha/beta

Descripción enfermedad:
Mucolipidosis type 2 alpha/beta follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the GNPTAB gene located on chromosomal region 12q23.2. The age of onset is infantile. This disease is characterized by growth retardation, short stature, skeletal abnormalities, facial dysmorphism, stiff skin, developmental delay and cardiomegaly and that is lethal in childhood. Mucolipidosis Type 3 is characterized clinically by short stature, skeletal abnormalities, cardiomegaly, and developmental delay. The disorder is caused by a defect in proper lysosomal enzyme phosphorylation and localization, which results in accumulation of lysosomal substrates. It is phenotypically less severe than the allelic disorder mucolipidosis type II alpha/beta. The prevalence is 1:123,500-1:625,500.

c.3741_3744delAGAA;c.3663delG;c.3613C>T;c.3603G>A;c.3603-1G>A;c.3569dupA;c.3565C>T;c.3560_3561delAG;c.3523_3529delATGTTCC;c.3503_3504delTC;c.3487_3490delACAG;c.3474_3475delTA;c.3458A>G;c.3449delT;c.3443_3446delTTTG;c.3435-1G>A;c.3434+1G>A;c.3428dupA;c.3410T>A;c.3336-1G>A;c.3336-1G>C;c.3335+6T>G;c.3335+1G>A;c.3330dupA;c.3326dupA;c.3310delG;c.3252delA;c.3250-1_3250delGCinsAT;c.3250-2A>G;c.3249+1G>A;c.3249+1G>C;c.3231_3234dupCTAC;c.3232delT;c.3173C>G;c.3145_3146insC;c.3091C>T;c.3061C>T;c.3053A>G;c.3002T>C;c.2956C>T;c.2918dupT;c.2896delA;c.2867A>G;c.2866C>T;c.2715+2T>G;c.2715+1G>A;c.2693delA;c.2693dupA;c.2681G>A;c.2664C>G;c.2659dupA;c.2617dupA;c.2614delG;c.2591_2592insG;c.2574_2575delGA;c.2550_2554delGAAAA;c.2544delA;c.2533C>T;c.2427delC;c.2422delC;c.2383delG;c.2369_2370delTT;c.2275_2276delAA;c.2249dupA;c.2220_2221dupGA;c.2189delT;c.2188delTinsAAA;c.2089dupC;c.2053_2057delTCAAC;c.1999_2000insT;c.1999G>T;c.1965delC;c.1959_1962delTAGT;c.1906dupA;c.1759C>T;c.1741_1742insTATATATA;c.1625_1626insC;c.1581delC;c.1519C>T;c.1514G>A;c.1408+1G>T;c.1402T>A;c.1399delG;c.1389_1390delGG;c.1385dupA;c.1381T>G;c.1331dupG;c.1325G>A;c.1298G>A;c.1285-2A>G;c.1220A>C;c.1208T>C;c.1206dupT;c.1196C>T;c.1191_1194dupGCTG;c.1123C>T;c.1120T>C;c.1090C>T;c.1036_1037delAT;c.1032delG;c.1017_1020dupTGCA;c.1001G>A;c.1001G>T;c.1000C>T;c.940C>T;c.933+1G>T;c.914dupA;c.857dupA;c.850delA;c.832C>T;c.771+2T>A;c.771+1G>C;c.755_759delCCTCT;c.749dupA;c.732_733delAA;c.648_651delAGAA;c.637-1G>A;c.625_629delAGGGG;c.616_619delACAG;c.517_518insA;c.441delC;c.377T>A;c.366-2A>G;c.344_345delCA;c.310C>T;c.242G>T;c.204-1G>C;c.171delA;c.168T>A;c.163dupT;c.157_160delTTTG;c.136C>T;c.121delG;c.118-2A>G;c.99delC;c.25C>T;c.10A>C

Mucopolysaccharidosis, type 3D (Sanfilippo syndrome D)

Descripción enfermedad:
Mucolipidosis type 3D (Sanfilippo disease) follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the GNS gene located on chromosomal region 12q14.3. The age of onset is infantile. This disease is characterized by joint stiffness and pain initially in the shoulders, hips, and fingers; and gradual mild coarsening of facial features, cardiorespiratory complications and mild cognitive impairment. The incidence is 1:70,000 newborn.

c.1226dupG;c.1169delA;c.1168C>T;c.1138_1139insGTCCT;c.1063C>T;c.413C>G;c.83delT

Ocular albinism, type 1 (Nettleship-Falls type)

Descripción enfermedad:
X-linked recessive ocular albinism follows an X-linked pattern of inheritance and is caused by pathogenic variants in the GPR143 gene located on chromosomal region Xp22.2. The age of onset is infantile. This condition reduces the coloring (pigmentation) of the iris, which is the colored part of the eye, and the retina, which is the light-sensitive tissue at the back of the eye. Pigmentation in the eye is essential for normal vision. Ocular albinism type I (OA1) is the most common form of ocular albinism. Clinical presentation of OA1 in Caucasians is characterized by nystagmus, impaired visual acuity, iris hypopigmentation with translucency, albinotic fundus, macular hypoplasia, and normally pigmented skin and hair. Carrier females usually have punctate iris translucency and a mottled pattern of fundus pigmentation. In contrast to Caucasian patients, black or Japanese patients with OA1 often have brown irides with little or no translucency and varying degrees of fundus hypopigmentation, the so-called 'nonalbinotic fundus' (summary by Xiao and Zhang, 2009). The prevalence is 1/60,000 to 1/150,000 live male births.

c.992_993insCG;c.768-1G>A;c.695C>A

Hyperoxaluria, primary, type 2

Descripción enfermedad:
Primary hyperoxaluria, type 2 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the GRHPR gene located on chromosomal region 9p13.2. The age of onset is infantile. This disease is characterized by recurrent nephrolithiasis, nephrocalcinosis and end-stage renal disease with subsequent systemic oxalosis.

c.45delA;c.84-2A>G;c.103delG;c.102G>A;c.154delG;c.188_189delTG;c.203T>C;c.214+1G>C;c.214+1G>T;c.214+2T>G;c.228dupA;c.248_249delTG;c.288-2_288delAGT;c.295C>T;c.337G>T;c.375delG;c.404+3_404+6delAAGT;c.404delA;c.405-1G>A;c.435_436delGC;c.435G>A;c.441_442delTG;c.454dupA;c.478G>A;c.493+2T>A;c.494G>A;c.515delT;c.540delT;c.597delT;c.598+1G>T;c.599-1G>C;c.608_609delCT;c.622C>T;c.694delC;c.735-1G>A;c.743T>A;c.755dupA;c.864_865delTG;c.904C>T;c.905G>A;c.934A>G;c.965T>C;c.965T>G

Mucopolysaccharidosis, type 7

Descripción enfermedad:
Mucopolysaccharidosis type 7 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the GUSB gene located on chromosomal region 7q11.21. The age of onset is variable. There are prenatal forms with non-immune hydrops fetalis, and severe neonatal forms with dysmorphism, hernias, hepatosplenomegaly, club feet, dysostosis, severe hypotonia and neurological disorders that ultimately lead to profound intellectual deficit and small stature in patients that survive. Finally, there are also very mild cases that are discovered during adolescence or adulthood following presentation with thoracic kyphosis. The prevalence is 1:250,000 in newborn.

c.1881G>T;c.1856C>T;c.1831C>T;c.1730G>T;c.1618G>T;c.1586A>G;c.1534G>A;c.1521G>A;c.1484A>G;c.1429C>T;c.1338G>A;c.1337G>A;c.1244+1G>A;c.1219_1220insC;c.1144C>T;c.1084G>A;c.1069C>T;c.1065+1G>T;c.1061C>T;c.1050G>C;c.959A>C;c.866G>A;c.820_821delAC;c.646C>T;c.530C>T;c.526C>T;c.499C>T;c.442C>T;c.398G>C;c.328C>T;c.307C>T

LCHAD deficiency

Descripción enfermedad:
Isolated deficiency of long-chain 3-hydroxyl-CoA dehydrogenase (LCHAD deficiency) follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the HADHA gene located on chromosomal region 2p23.3. This disease is characterized in infancy/early childhood of hypoketotic hypoglycemia, metabolic acidosis, liver disease, hypotonia and, frequently, cardiac involvement with arrhythmias and/or cardiomyopathy. The prevalence is 1/250,000.

c.2225_2228dupAACA;c.2220T>A;c.2146+2T>C;c.2146+1G>A;c.2132dupC;c.2114T>A;c.2071G>T;c.2059delA;c.2000+1G>C;c.1967delT;c.1959dupT;c.1916_1919dupATCA;c.1915_1918delTATC;c.1918C>T;c.1814_1815delAA;c.1811delG;c.1793_1794delAT;c.1690-2A>G;c.1678C>T;c.1668_1674dupTGAAGTC;c.1644delC;c.1620+2_1620+6delTAAGG;c.1590delC;c.1528G>C;c.1479+1G>T;c.1422dupT;c.1344_1345delGT;c.1237A>T;c.1221-1G>C;c.1202delA;c.1195C>T;c.1132C>T;c.1086-3_1092delCAGGCATCTG;c.1052delA;c.1025T>C;c.919-2A>G;c.914T>A;c.871C>T;c.844_845insA;c.845T>A;c.800-1_801delGAA;c.800-1G>T;c.703C>T;c.677-1G>A;c.676+2T>C;c.515delC;c.499delA;c.453+1G>A;c.315-1G>A;c.274_278delTCATC;c.240G>A;c.180_180+5delGGTATCinsAT;c.180+3A>G;c.180+1G>A;c.157C>T;c.72delT

Trifunctional protein deficiency

Descripción enfermedad:
Mitochondrial trifunctional protein deficiency follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in HADHB gene located on chromosomal region 2p23.3. The age of onset is neonatal/infancy. It is characterized by a wide clinical spectrum ranging from severe neonatal manifestations including cardiomyopathy, hypoglycemia, metabolic acidosis, skeletal myopathy and neuropathy, liver disease and death to a mild phenotype with peripheral polyneuropathy, episodic rhabdomyolysis and pigmentary retinopathy. The prevalence is <1 / 1,000,000.

c.182G>A;c.209+1G>A;c.210-1G>T;c.254+1G>A;c.357dupT;c.685C>T;c.740G>A;c.788A>G;c.1059delT;c.1175C>T;c.1211dupG;c.1331G>A;c.1364T>G

Neutropenia, severe congenital, type 3, autosomal recessive

Descripción enfermedad:
Neutropenia, severe congenital, type 3 is an autosomal recessive bone marrow failure disorder characterized by low numbers of neutrophils, increased susceptibility to bacterial and fungal infections, and increased risk of developing myelodysplastic syndrome or acute myeloid leukemia. In addition, patients with HAX1 mutations affecting both isoform A and B of the gene develop neurologic abnormalities (Boztug et al., 2010).The Swedish physician Rolf Kostmann (1956) described an autosomal recessive hematologic disorder, termed infantile agranulocytosis, with severe neutropenia with an absolute neutrophil count below 0.5 x 10(9)/l and early onset of severe bacterial infections. The disorder was later termed Kostmann syndrome (Skokowa et al., 2007). Lekstrom-Himes and Gallin (2000) discussed severe congenital neutropenia in a review of immunodeficiencies caused by defects in phagocytes.In addition to Kostmann agranulocytosis, recessively inherited neutropenic syndromes include congenital neutropenia with eosinophilia (257100), Chediak-Higashi syndrome (214500), and Fanconi pancytopenic syndrome (227650).

c.91delG;c.256C>T;c.430dupG;c.568C>T

Thalassemia, alpha-

Descripción enfermedad:
Alpha-thalassemia follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the HBA1 gene located on chromosomal region 16p13.3. The age of onset is infantile. It is characterized by impaired synthesis of alpha-globin chains leading to a variable clinical picture depending on the number of affected alleles. The disease can be classified into clinical subtypes of increasing severity: silent alpha thalassemia, alpha thalassemia trait (or alpha thalassemia minor), hemoglobin H disease (HbH), and Hb Bart's hydrops fetalis (see these terms). A rare form called alpha-thalassemia-intellectual deficit syndrome has also been identified (see these terms). Alpha thalassemia trait causes microcytosis and hypochromia with absent or mild anemia (often detected on routine blood tests), generally with no other symptoms. HbH patients develop moderate hemolytic anemia with variable amounts of HbH along with occasionally severe splenomegaly, sometimes complicated by hypersplenism. Hb Bart's hydrops fetalis involves a severe deficiency in alpha-globin with serious developmental implications. Alpha-thalassemia-intellectual deficit syndrome is characterized by very mild to severe anemia associated with developmental abnormalities. The prevalence is 1:10,000-5:10,000.

--FIL;--MED;--SEA;--THAI;-(α)20.5;-α3.7;-α4.2

Thalassemia, alpha-

Descripción enfermedad:
Alpha-thalassemia follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the HBA2 gene located on chromosomal region 16p13.3. The age of onset is infantile. It is characterized by impaired synthesis of alpha-globin chains leading to a variable clinical picture depending on the number of affected alleles. The disease can be classified into clinical subtypes of increasing severity: silent alpha thalassemia, alpha thalassemia trait (or alpha thalassemia minor), hemoglobin H disease (HbH), and Hb Bart's hydrops fetalis (see these terms). A rare form called alpha-thalassemia-intellectual deficit syndrome has also been identified (see these terms). Alpha thalassemia trait causes microcytosis and hypochromia with absent or mild anemia (often detected on routine blood tests), generally with no other symptoms. HbH patients develop moderate hemolytic anemia with variable amounts of HbH along with occasionally severe splenomegaly, sometimes complicated by hypersplenism. Hb Bart's hydrops fetalis involves a severe deficiency in alpha-globin with serious developmental implications. Alpha-thalassemia-intellectual deficit syndrome is characterized by very mild to severe anemia associated with developmental abnormalities. The prevalence is 1:10,000-5:10,000.

--FIL;--MED;--SEA;--THAI;-(α)20.5;-α3.7;-α4.2

HBB-related hemoglobinopathy

Descripción enfermedad:
DNA variations in the HBB gene result in the production of different versions of beta-globin. Some of these variations may affect a person's health while other variations cause no noticeable signs or symptoms. Two of the most common HBB-related conditions are beta-thalassemia and sickle cell anemia (SCA). Beta thalassemia is caused by HBB gene mutations that prevent or decrease beta-globin production, subunits that make up hemoglobin. A lack of hemoglobin disrupts the normal development of red blood cells. A shortage of mature red blood cells can reduce the amount of oxygen that is delivered to tissues to below what is needed to satisfy the body's energy needs. A lack of oxygen in the body's tissues can lead to poor growth, organ damage, and other health problems associated with beta thalassemia. SCA is a multisystem disease associated with episodes of acute illness and progressive organ damage. SCA-associated mutations cause red blood cells assuming an abnormal, rigid, sickle shape promoting cell break down prematurely, which can lead to anemia. Anemia can cause shortness of breath, fatigue, and delayed growth and development in children.

c.*110T>C;c.440_441dupAC;c.440A>C;c.440A>T;c.439C>G;c.438T>A;c.437A>G;c.436T>C;c.435G>C;c.431A>C;c.428C>A;c.421G>A;c.383A>C;c.371_378delCCCCACCA;c.364G>A;c.364G>T;c.347C>A;c.343_344delCTinsG;c.344T>C;c.341T>A;c.332T>C;c.328delG;c.328G>A;c.323dupG;c.320T>G;c.316-1G>A;c.316-1G>T;c.316-2A>C;c.316-2A>G;c.316-3C>A;c.316-106C>G;c.316-146T>G;c.316-197C>T;c.315+2T>G;c.315+1G>A;c.315+1G>C;c.312C>G;c.306G>C;c.305A>G;c.304G>A;c.302C>T;c.299A>C;c.299A>G;c.299A>T;c.298G>A;c.298G>C;c.298G>T;c.295G>A;c.293A>T;c.287dupA;c.282_283dupTG;c.283G>C;c.277C>A;c.277C>T;c.275T>C;c.271G>T;c.269G>A;c.268A>C;c.257T>C;c.251delG;c.248A>C;c.248A>T;c.247A>G;c.230delC;c.226delC;c.217_221delAGTGAinsT;c.217dupA;c.216dupT;c.208G>A;c.206T>A;c.203_204delTG;c.201delA;c.199A>G;c.194delG;c.190C>T;c.184A>T;c.182T>A;c.179A>C;c.176C>G;c.162delT;c.143_146dupATCT;c.143dupA;c.135delC;c.134C>G;c.126_129delCTTT;c.130G>T;c.128T>C;c.127T>C;c.127T>G;c.114_120delGACCCAG;c.117_118delCC;c.118C>T;c.114G>A;c.112delT;c.113G>A;c.110delC;c.108C>A;c.103G>T;c.93G>T;c.93-1G>A;c.93-1G>C;c.93-2A>C;c.93-21G>A;c.92+6T>C;c.92+5G>A;c.92+5G>C;c.92+5G>T;c.92+2T>A;c.92+2T>C;c.92+1G>A;c.92+1G>T;c.92G>A;c.92G>C;c.91A>C;c.90C>T;c.85dupC;c.86T>A;c.82G>T;c.79_80insT;c.80A>G;c.79G>A;c.79G>T;c.68_74delAAGTTGG;c.75T>A;c.64dupG;c.59A>G;c.51delC;c.52A>T;c.48G>A;c.46delT;c.47G>A;c.45dupG;c.36delT;c.27dupG;c.25_26delAA;c.20delA;c.20A>T;c.17_18delCT;c.19G>A;c.8A>C;c.4delG;c.4G>T;c.3G>A;c.2T>A;c.2T>C;c.2T>G;c.1A>G;c.-50A>C;c.-75G>C;c.-78A>C;c.-78A>G;c.-79A>G;c.-80T>A;c.-137C>A;c.-137C>G;c.-138C>T;c.-151C>T

Tay-Sachs disease

Descripción enfermedad:
Tay-Sachs disease follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the HEXA gene located on chromosomal region 15q23. The age of onset is infantile. There are three forms, type 1 (infantile), with a psychomotor retardation which is associated with hypotonia, amaurosis and megalencephaly. Type 2 is characterized by locomotor ataxia, behavioural disorders, and progressive loss of intellectual capacities. Type three (chronic form) shows spinocerebellar ataxia or spinal amyotrophy. The prevalence is 1 case per 320 000 live births.

c.1570C>T;c.1561C>T;c.1559+2T>C;c.1559+1G>T;c.1543delC;c.1544G>A;c.1543C>T;c.1535C>G;c.1532delT;c.1529G>A;c.1528C>T;c.1487G>A;c.1477G>A;c.1465G>A;c.1455G>C;c.1455-1G>T;c.1454+1G>C;c.1454+1G>T;c.1454G>A;c.1418A>T;c.1393G>A;c.1382delC;c.1363+1G>A;c.1340_1341delTA;c.1338C>T;c.1311_1312insTATC;c.1307_1310dupTATC;c.1293G>C;c.1292G>A;c.1247_1248delAAinsG;c.1211G>C;c.1210C>T;c.1209G>A;c.1201C>T;c.1183C>T;c.1173delA;c.1156delG;c.1154A>C;c.1106+1G>A;c.1106+1G>T;c.1076_1079delTCAA;c.1020G>A;c.1019+3A>G;c.997G>A;c.997G>T;c.980dupA;c.962_963delCT;c.948_950delCTT;c.931_938delTTCATGAG;c.935T>G;c.839-1G>C;c.838+1G>A;c.838+1G>C;c.838G>A;c.838G>C;c.821C>T;c.805G>C;c.782G>A;c.751_752insT;c.742C>T;c.705+1G>A;c.665T>C;c.662C>T;c.604-1G>T;c.603+1G>A;c.584_585delCT;c.573C>G;c.571T>C;c.569A>G;c.566G>A;c.566G>T;c.565C>T;c.557A>C;c.542G>A;c.541C>T;c.498delT;c.493-1G>A;c.493-1G>T;c.492+5G>A;c.469delG;c.459delT;c.442C>T;c.413T>G;c.379+1G>A;c.379+1G>C;c.379+1G>T;c.373G>A;c.349C>T;c.254-1G>C;c.253+1G>A;c.187G>T;c.173G>A;c.155C>A;c.116T>G;c.78G>A;c.77G>A;c.2T>C;c.1A>G;c.1A>T

Sandhoff disease, infantile, juvenile, and adult forms

Descripción enfermedad:
Sandhoff disease follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the HEXB gene located on chromosomal region 5q13.3. The age of onset is adult or infantile. This disease is characterized by central nervous system degeneration, with startle reactions, early blindness, progressive motor and mental deterioration, macrocephaly and cherry-red spots on the macula. The prevalence is 1/130.000.

c.115delG;c.146C>A;c.171delG;c.170G>A;c.202_203insGG;c.298delC;c.299+1G>A;c.300-1G>A;c.333G>A;c.508C>T;c.512-1G>T;c.552T>G;c.796T>G;c.797A>G;c.825delT;c.841C>T;c.850C>T;c.902-1G>T;c.965delT;c.1023_1026delTGAG;c.1082+5G>A;c.1238_1242delCAAAG;c.1243-2A>G;c.1250C>T;c.1305_1306delAG;c.1310_1311delCA;c.1345delT;c.1375G>T;c.1380G>A;c.1389C>G;c.1417G>A;c.1509-26G>A;c.1510C>T;c.1514G>A;c.1517_1529dupCAAGTGCTGTTGG;c.1535_1536delGA;c.1539_1540delCT;c.1559_1562dupGAGA;c.1597C>T;c.1611_1613+2delCGAGT

Alkaptonuria

Descripción enfermedad:
Alkaptonuria follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the HGD gene located on chromosomal region 3q13.33. The age of onset is infantile. This disease is characterized by darkening of the urine when it is left exposed to air, grey-blue colouration of the eye sclerae and the ear helix (ochronosis), and a disabling joint disease involving both the axial and peripheral joints (ochronotic arthropathy). The prevalence is 1:250,000-1:1.000.000 newborn.

c.1336T>C;c.1201G>C;c.1189-2A>G;c.1188+1G>T;c.1111dupC;c.1112A>G;c.1102A>G;c.1064dupG;c.1017_1019delGAGinsTA;c.990G>T;c.970dupG;c.956delC;c.899T>G;c.879+1G>A;c.808G>A;c.781dupT;c.688C>T;c.674G>A;c.652delG;c.649+2T>C;c.481G>A;c.469+2T>C;c.457dupG;c.409delC;c.390delG;c.376_377delAA;c.365C>T;c.360T>G;c.346delC;c.339_342+2delGAGTGT;c.342+1G>A;c.342+1G>T;c.179G>A;c.177-1G>A;c.175delA;c.172A>T;c.158G>A;c.140C>T;c.58delC;c.31_32delGGinsATT;c.16-1G>A;c.15+1G>A;c.11T>A

Mucopolysaccharidosis type 3C (Sanfilippo syndrome C)

Descripción enfermedad:
Mucopolysaccharidosis type 3C (Sanfilippo C) follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the HGSNAT gene located on chromosomal region 8p11.21. The age of onset is infantile. This disease is characterized by defective or missing enzymes to break down mucopolysaccharides are missing or are defective. The prevalence is <1:70.000 newborn.

c.234+1G>A;c.372-2A>G;c.493+1G>A;c.525dupT;c.607C>T;c.739delA;c.744-2A>G;c.848C>T;c.851+1G>A;c.851+1G>T;c.852-2A>C;c.852-1G>A;c.887C>A;c.947G>A;c.962T>G;c.1030C>T;c.1102A>T;c.1129-2A>T;c.1150C>T;c.1250+1G>A;c.1360C>T;c.1378-1G>A;c.1411G>A;c.1464+1G>A;c.1503delA;c.1516C>T;c.1542+1G>A;c.1542+1G>C;c.1542+2T>G;c.1553C>T;c.1614-2A>T;c.1622C>T;c.1674C>G

Holocarboxylase synthetase deficiency

Descripción enfermedad:
Holocarboxylase synthetase deficiency, a biotin-responsive multiple carboxylase deficiency (MCD), is characterized by metabolic acidosis, lethargy, hypotonia, convulsions, and dermatitis. Most patients present in the newborn or early infantile period, but some become symptomatic in the later infantile period (Suzuki et al., 2005). Care must be taken to differentiate the inherited multiple carboxylase deficiencies from acquired biotin deficiencies, such as those that develop after excessive dietary intake of avidin, an egg-white glycoprotein that binds specifically and essentially irreversibly to biotin (Sweetman et al., 1981) or prolonged parenteral alimentation without supplemental biotin (Mock et al., 1981).

c.1993C>T;c.1892delT;c.1741G>A;c.1693C>T;c.1680+1G>A;c.1648G>A;c.1624C>T;c.1522C>T;c.1258_1259delCT;c.1180-2A>G;c.1179+1G>A;c.1135C>T;c.782delG;c.655dupA;c.604G>T;c.416T>A;c.271_272delAG;c.250G>T;c.128_144delCGAAGCCTGAACCTTCTinsTTGCTTGAGATTAAGCCTGAGATTAAGG

HMG-CoA lyase deficiency

Descripción enfermedad:
3-hydroxy-3-methylglutaric aciduria follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the HMGCL gene located on chromosomal region 1p36.11. The age of onset is infantile. This disease is is an organic aciduria, due to deficiency of 3-hydroxy-3-methylglutaryl-CoA-lyase (a key enzyme in ketogenesis and leucine metabolism) usually presenting in infancy with episodes of metabolic decompensation triggered by periods of fasting or infections, which when left untreated are life-threatening and may lead to neurological sequelae.

c.914_915delTT;c.863T>A;c.835G>A;c.804C>A;c.698A>G;c.562-2A>G;c.505_506delTC;c.497+4A>G;c.286C>T;c.230delT;c.206_207delCT;c.122G>A;c.121C>T;c.109G>T;c.60+1G>T;c.31C>T;c.27delG

Hermansky-Pudlak syndrome, type 1

Descripción enfermedad:
Hermansky-Pudlak syndrome, type 1 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the HPS1 gene located on chromosomal region 10q24.2. The age of onset is early childhood. This disease is characterized by oculocutaneous albinism, bleeding diathesis and, in some cases, neutropenia, pulmonary fibrosis, or granulomatous colitis. The prevalence is 1/500,000 - 1/1,000,000.

c.1996G>T;c.1749G>A;c.1744-2A>C;c.1691delA;c.1395G>A;c.1375delA;c.1323dupA;c.1189delC;c.974_975insC;c.972delC;c.972dupC;c.962delG;c.962dupG;c.932delG;c.532dupC;c.418delG;c.398+5G>A;c.398+2T>C;c.397G>T;c.391C>T;c.355delC;c.288delT;c.233_242delACTTCCTGTA

Hermansky-Pudlak syndrome 3

Descripción enfermedad:
Hermansky-Pudlak syndrome 3 (HPS3) is a form of Hermansky-Pudlak syndrome (HPS), a genetically heterogeneous autosomal recessive disorder characterized by oculocutaneous albinism, bleeding due to platelet storage pool deficiency, and lysosomal storage defects. This syndrome results from defects of diverse cytoplasmic organelles including melanosomes, platelet dense granules and lysosomes. Ceroid storage in the lungs is associated with pulmonary fibrosis, a common cause of premature death in individuals with HPS.

c.1163+1G>A;c.1691+2T>G;c.2482-2A>G;c.2589+1G>C

D-bifunctional protein deficiency

Descripción enfermedad:
Bifunctional enzyme deficiency follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the HSD17B4 gene located on chromosomal region 5q23. The age of onset is juvenile. This disease is characterized by slowly progressive cerebellar atrophy and ataxia, intellectual decline, hearing loss, hypogonadism, hyperreflexia, a demyelinating sensorimotor neuropathy.

c.46G>A;c.68+2T>A;c.67C>T;c.188-1G>T;c.295+2T>C;c.296-1G>C;c.345delT;c.356-2A>G;c.371dupA;c.392G>C;c.424+1G>T;c.442C>G;c.469C>T;c.510-2A>T;c.601A>G;c.682_685delACAG;c.698-1G>A;c.698-1G>T;c.725A>G;c.784_787delTTTG;c.817C>T;c.947C>G;c.1011_1012delTA;c.1047+1G>T;c.1048-2A>C;c.1285-1G>A;c.1343T>G;c.1375_1378delGATA;c.1409-2A>T;c.1444A>G;c.1444A>T;c.1513-2A>C;c.1513-1G>A;c.1515_1516delAG;c.1579-2A>C;c.1622T>C;c.1649-1G>A;c.1705_1708dupGTGT;c.1771_1777delCCAGTATinsAA;c.1792_1793delCT;c.1823_1824delGA;c.1982delA;c.2011_2015delGTAAA;c.2068+2T>G;c.2069-2A>G;c.2104C>T;c.2196+1G>C

Dyssegmental dysplasia, Silverman-Handmaker type

Descripción enfermedad:
Dyssegmental dysplasia, Silverman-Handmaker type follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the HSPG2 gene located on chromosomal region 1p36.12. The age of onset is prenatal/neonatal. This disease is characterized by anisospondyly, severe short stature and limb shortening, metaphyseal flaring and distinct dysmorphic features (i.e. flat facial appearance, abnormal ears, short neck, narrow thorax). Additional features may include other skeletal findings (e.g. joint contractures, bowed limbs, talipes equinovarus) and urogenital and cardiovascular abnormalities. The prevalence is below 1/1,000,000.

c.13078delC;c.10897C>T;c.9329delA;c.8467+4A>G;c.7009+1G>A;c.4598G>A;c.2042_2043delCG;c.1791G>A;c.1656_1657insT;c.1125C>A

Hydrolethalus syndrome

Descripción enfermedad:
Hydrolethalus syndrome follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the HYLS1 gene located on chromosomal region 11q24.2. The age of onset is fetal. This disease is characterized by craniofacial dysmorphic features, central nervous system, cardiac, respiratory tract and limb abnormalities. The incidence is 1/20,000 in Finland and the prevalence is <1:1,000,000.

c.632A>G;c.669G>A;c.724C>T

Mucopolysaccharidosis, type 2

Descripción enfermedad:
Mucopolysaccharidosis, type 2 follows an X-linked pattern of inheritance and is caused by pathogenic variants in the IDS gene located on chromosomal region Xq28. The age of onset is infantile. This disease is characterized by distinctive coarse facial features, short stature, cardio-respiratory involvement and skeletal abnormalities. The prevalence is 1:100,000-1:170,000 mannewborn.

c.1591C>T;c.1508T>A;c.1505G>C;c.1463delT;c.1425G>A;c.1403G>A;c.1403G>C;c.1403G>T;c.1402C>T;c.1393C>T;c.1327C>T;c.1265G>A;c.1265G>T;c.1264T>G;c.1181-1G>A;c.1148delC;c.1132_1133delTT;c.1122C>T;c.1106C>A;c.1046G>A;c.1033T>A;c.1025A>C;c.1016T>C;c.1006+1G>T;c.1003C>T;c.998C>T;c.935G>A;c.908_909delCT;c.884A>T;c.880-8A>G;c.832_833insATGTTTAAGGGAAG;c.820G>T;c.806A>T;c.754_767delGATCCCGAGGTCCC;c.708+1G>A;c.702C>A;c.690_691insT;c.688A>T;c.683C>A;c.683C>T;c.613G>C;c.596_599delAACA;c.597delA;c.592G>A;c.587T>C;c.514C>T;c.509_510delCA;c.508-1G>A;c.508-1G>C;c.476_478delATC;c.479C>A;c.479C>G;c.469C>T;c.463_464delTTinsCCGTATAGCTGG;c.425C>A;c.419-1G>A;c.411delT;c.404A>G;c.401G>A;c.388_389insG;c.359C>A;c.349_351delTCC;c.314_317dupTCAA;c.309C>G;c.15-2A>G;c.278delC;c.262C>T;c.253G>A;c.252C>A;c.240+1G>A;c.208dupC;c.196C>T;c.181T>C;c.133G>C;c.103+1G>C

Mucopolysaccharidosis, type 1H; Mucopolysaccharidosis, type 1H/S; Mucopolysaccharidosis, type 1S

Descripción enfermedad:
The mucopolysaccharidoses type 1 are a group of inherited disorders caused by a lack of specific lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs), or mucopolysaccharides. The accumulation of partially degraded GAGs causes interference with cell, tissue, and organ function.Deficiency of alpha-L-iduronidase can result in a wide range of phenotypic involvement with 3 major recognized clinical entities: Hurler (MPS1H), Scheie (MPS1S), and Hurler-Scheie (MPS1H/S) syndromes. Hurler and Scheie syndromes represent phenotypes at the severe and mild ends of the MPS1 clinical spectrum, respectively, and the Hurler-Scheie syndrome is intermediate in phenotypic expression (McKusick, 1972). MPS1 is more frequent than MPS2 (Hunter syndrome; 309900), which has no corneal clouding and pursues a slower course.

c.46_57delTCGCTCCTGGCC;c.53T>C;c.152G>A;c.158+1G>A;c.159-1G>A;c.164delC;c.191_192delAC;c.192C>A;c.208C>T;c.266G>A;c.299+1G>T;c.300-1G>A;c.385+1G>C;c.386-2A>G;c.488dupA;c.493+1G>A;c.494-1G>A;c.494-1G>C;c.501C>G;c.523T>C;c.542dupA;c.589+1G>A;c.606C>A;c.612_615dupCTGC;c.613_617dupTGCTC;c.653T>C;c.713T>A;c.793-1G>A;c.820G>T;c.876delC;c.928C>T;c.972+1G>A;c.979G>C;c.1029C>A;c.1029C>G;c.1037T>G;c.1045G>A;c.1091C>T;c.1096A>C;c.1163C>A;c.1163C>G;c.1190-2A>T;c.1205G>A;c.1206G>A;c.1210G>T;c.1402+1G>A;c.1402+1G>C;c.1402+2T>G;c.1469T>C;c.1487C>G;c.1524+1G>T;c.1591delC;c.1598C>G;c.1602delG;c.1614delG;c.1650+5G>A;c.1728-2A>G;c.1728-1G>C;c.1743C>G;c.1799delC;c.1828+1G>C;c.1829-2A>G;c.1829-1G>A;c.1854C>A;c.1855C>T;c.1861C>T;c.1874A>G;c.1882C>T;c.1893delC

Charcot-Marie-Tooth disease, axonal, type 2S

Descripción enfermedad:
Charcot-Marie-Tooth disease, axonal, type 2S follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the IGHMBP2 gene located on chromosomal region 11q13.3. The age of onset can be infancy, childhood, adult or adolescent. This disease is characterized by progressive distal muscle weakness and atrophy of both the lower and upper limbs, absent or reduced deep tendon reflexes, mild sensory loss, foot drop, and pes cavus leading eventually to wheelchair dependence. Some patients present with early hypotonia and delayed motor development. Scoliosis and variable autonomic disturbances may be associated. The prevalence is below 1/1,000,000.

c.2T>C;c.92G>A;c.121C>T;c.127C>T;c.138T>A;c.257-2A>G;c.292_303delGGCAGTCAGCTGinsATGCT;c.439C>T;c.449+1G>A;c.449+1G>T;c.547+1G>A;c.638A>G;c.661delA;c.675delT;c.707T>G;c.826C>T;c.904C>T;c.958C>T;c.983_987delAAGAA;c.1060+2T>C;c.1082T>C;c.1107C>G;c.1118T>G;c.1193C>A;c.1346delT;c.1418+1G>C;c.1478C>T;c.1488C>A;c.1516G>T;c.1540G>A;c.1582G>A;c.1633-2A>G;c.1708C>T;c.1738G>A;c.1813C>T;c.2197_2203delATAGTGGinsCA;c.2362C>T;c.2368C>T;c.2560C>T;c.2575C>T;c.2598_2599delGA;c.2611+1G>T;c.2784+1G>T;c.2911_2912delAG

Severe combined immunodeficiency, X-linked

Descripción enfermedad:
Severe combined immunodeficiency, X-linked follows an X-linked pattern of inheritance and is caused by pathogenic variants in the IL2RG gene located on chromosomal region Xq13.1. The age of onset is infantile. This disease is characterized by absent or markedly reduced numbers of T cells, leading to recurrent infections. The prevalence is 1:50,000-1:100,000.

c.982C>T;c.924+1G>A;c.923C>A;c.878T>A;c.865C>T;c.855-1G>A;c.854G>A;c.846G>A;c.758-1G>A;c.718T>C;c.703_711dupCAGCATTGG;c.710G>A;c.703C>T;c.677G>A;c.676C>T;c.664C>T;c.602C>G;c.562C>T;c.522G>A;c.467C>T;c.458T>A;c.455T>C;c.454+1G>A;c.452T>C;c.421C>T;c.391C>T;c.355A>T;c.343T>C;c.341G>A;c.328delG;c.314A>G;c.281C>A;c.270G>A;c.270-1G>T;c.270-15A>G;c.202G>A;c.186T>A;c.2T>C

Isovaleric acidemia

Descripción enfermedad:
Isovaleric academia follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the IVD gene located on chromosomal region 15q15.1. The age of onset is neonatal. This disease is characterized by vomiting, dehydration, coma and abnormal movements. The prevalence is 1/100,000.

c.2T>G;c.111_112delCG;c.134T>C;c.153+1G>A;c.157C>T;c.158G>A;c.158G>C;c.166_169dupATGG;c.241C>T;c.243+1G>A;c.296-1G>A;c.358C>T;c.367G>A;c.390delT;c.406_407delTG;c.434_437dupATGA;c.465+2T>C;c.466-3_466-2delCAinsGG;c.466-2A>G;c.478_479insGT;c.507delG;c.559+1G>A;c.560-1G>A;c.593G>A;c.605G>T;c.627delT;c.720dupT;c.753dupT;c.793+1G>A;c.794-1G>A;c.879dupG;c.887+1G>A;c.899C>T;c.941C>T;c.970-2A>G;c.970-1G>T;c.994_995delAT;c.1117C>T;c.1141T>C;c.1145_1147+4delTTGGTGA;c.1183C>T;c.1188delT;c.1192C>T;c.1193G>A;c.1208A>G;c.1214T>C

Hyperinsulinemic hypoglycemia, type 2 (congenital hyperinsulinism); Permanent neonatal diabetes mellitus (PNDM)

Descripción enfermedad:
Hyperinsulinemic hypoglycemia, also referred to as congenital hyperinsulinism, nesidioblastosis, or familial hyperinsulinism, is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur (Thornton et al., 1998). More than 30 mutations in the KCNJ1 gene have been found to cause congenital hyperinsulinism.
Futhermore, around 30 mutations in the KCNJ1 gene have been found to cause permanent neonatal diabetes mellitus (PNDM). Permanent neonatal diabetes mellitus is a type of diabetes that first appears within the first 6 months of life and persists throughout the lifespan. This form of diabetes is characterized by high blood sugar levels (hyperglycemia) resulting from a shortage of the hormone insulin. Individuals with PNDM experience slow growth before birth (intrauterine growth retardation). Affected infants have hyperglycemia and an excessive loss of fluids (dehydration) and are unable to gain weight and grow at the expected rate (failure to thrive). In some cases, people with PNDM also have certain neurological problems, including developmental delay and recurrent seizures (epilepsy). This combination of developmental delay, epilepsy, and neonatal diabetes is called DEND syndrome. Intermediate DEND syndrome is a similar combination but with milder developmental delay and without epilepsy. A small number of individuals with PNDM have an underdeveloped pancreas. Because the pancreas produces digestive enzymes as well as secreting insulin and other hormones, affected individuals experience digestive problems such as fatty stools and an inability to absorb fat-soluble vitamins.

c.1001G>A;c.997T>A;c.989A>G;c.964G>A;c.902G>A;c.886A>C;c.881C>T;c.868G>A;c.866G>T;c.844G>A;c.776A>G;c.761C>T;c.755T>C;c.685G>A;c.679G>A;c.602G>A;c.602G>T;c.601C>T;c.544A>G;c.536A>C;c.521C>G;c.510G>C;c.509A>G;c.499A>C;c.497G>A;c.497G>T;c.175G>A;c.158G>A;c.157G>A;c.157G>C;c.154C>T;c.149G>A;c.36C>A;c.-134G>T

L1 Syndrome

Descripción enfermedad:
L1 syndrome describes a group of conditions that primarily affect the nervous system and occur almost exclusively in males. These conditions vary in severity and include, from most severe to least, X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS), MASA syndrome, spastic paraplegia type 1, and X-linked complicated corpus callosum agenesis. HSAS is an acronym for the characteristic features of the condition: fluid in the brain (hydrocephalus), muscle stiffness (spasticity), thumbs that are permanently bent toward the palms (adducted thumbs), and narrowing (stenosis) of the aqueduct of Sylvius in the brain. Individuals with HSAS often have severe intellectual disability and may have seizures. MASA syndrome include intellectual disability (mental retardation), mild to moderate, delayed speech (aphasia), spasticity, and adducted thumbs. Individuals with MASA syndrome may have mild enlargement of the ventricles. Spastic paraplegia type 1 is characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the limbs (paraplegia). Affected individuals also have mild to moderate intellectual disability. X-linked complicated corpus callosum agenesis is defined by underdevelopment (hypoplasia) or absence (agenesis) of the tissue that connects the left and right halves of the brain (the corpus callosum). The life expectancy of individuals with L1 syndrome varies depending on the severity of the signs and symptoms.

c.3581C>T;c.3489_3490delTG;c.3458-1G>C;c.3201T>G;c.3071C>G;c.3046+1G>C;c.2974C>T;c.2879delA;c.2547+1G>A;c.2544C>A;c.2438dupA;c.2433C>A;c.2421_2422delTG;c.2380C>T;c.2351A>G;c.2278C>T;c.2254G>A;c.2205G>A;c.2137+1G>A;c.2092G>A;c.2014C>T;c.1983delA;c.1939+1G>A;c.1939A>T;c.1792G>A;c.1780delA;c.1767C>A;c.1704-1G>A;c.1672C>T;c.1485C>G;c.1453C>T;c.1417C>T;c.1408C>T;c.1379G>A;c.1354G>A;c.1267+1G>A;c.1267C>T;c.1146C>G;c.1108G>A;c.998C>G;c.992-2A>G;c.924C>T;c.807-6G>A;c.806+1G>C;c.800dupA;c.791G>A;c.772C>T;c.719C>T;c.551G>A;c.536T>G;c.266C>A;c.177delC;c.26G>A;c.23delT

LAMA2-related muscular dystrophy

Descripción enfermedad:
LAMA2-related muscular dystrophy 1A follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the LAMA2 gene located on chromosomal region 6q22.33. LAMA2-related muscular dystrophy is a disorder that causes weakness and atrophy of skeletal muscles. This condition varies in severity, from a severe, early-onset type to a milder, late-onset form. Early-onset LAMA2-related muscular dystrophy is apparent at birth or within the first few months of life, called merosin-deficient congenital muscular dystrophy type 1A (607855). Patients show hypotonia, poor suck and cry, and delayed motor development; most never achieve independent ambulation. Most patients also have periventricular white matter abnormalities on brain imaging, but mental retardation and/or seizures occur only rarely. Symptoms of late-onset LAMA2-related muscular dystrophy become evident later in childhood or adulthood, and are similar to those of a group of muscle disorders classified as autosomal recessive limb-girdle muscular dystrophies, type 23. This group is characterized by slowly progressive proximal muscle weakness primarily affecting the lower limbs and resulting in gait difficulties. Additional features include white matter abnormalities on brain imaging, increased serum creatine kinase, and dystrophic features, with partial LAMA2 deficiency on muscle biopsy. Some patients may have additional neurologic features, including executive deficits, seizures, and peripheral neuropathy. Patients remain ambulatory well into adulthood. The prevalence is 1/30,000.

c.2T>C;c.112+1G>A;c.184G>T;c.283C>T;c.283+1G>A;c.329G>A;c.363C>A;c.391C>T;c.396+1G>T;c.444dupG;c.498G>A;c.524_534dupAGTGCCTAACG;c.640-1G>A;c.817A>T;c.819+1G>A;c.819+2T>C;c.825delC;c.828C>G;c.939_940delAT;c.1027+1G>A;c.1027+1G>T;c.1028-1G>A;c.1032_1042delCAATTGTCATG;c.1050delT;c.1122delA;c.1303C>T;c.1306+2T>G;c.1307-1G>A;c.1467+1G>A;c.1467+1G>T;c.1467+2T>C;c.1610_1611delTA;c.1612C>T;c.1657C>T;c.1762delG;c.1854_1861dupACGTGTTC;c.1855_1856insATGTTCAC;c.2049_2050delAG;c.2096+1G>A;c.2098_2099delTT;c.2230C>T;c.2322+1G>C;c.2323-2A>T;c.2323-1G>A;c.2350dupT;c.2352T>G;c.2451-2A>G;c.2556delT;c.2749+1G>A;c.2749+1G>C;c.2750-1G>C;c.2836C>T;c.2901C>A;c.2962C>T;c.3085C>T;c.3215delG;c.3237C>A;c.3283C>T;c.3294delG;c.3555+1G>A;c.3630delT;c.3636delT;c.3718C>T;c.3736-2A>G;c.3736-2A>T;c.3829C>T;c.3924+2T>C;c.3976C>T;c.3979_3985dupGAAGACT;c.4048C>T;c.4176+1G>A;c.4198C>T;c.4348C>T;c.4436+1G>C;c.4523+1G>A;c.4524-2A>T;c.4645C>T;c.4692_4695dupTGCA;c.4717+1G>C;c.4717+1G>T;c.4860+2delTinsGGCC;c.4876C>T;c.4960-2A>G;c.5050G>T;c.5116C>T;c.5156_5159delAAGA;c.5227G>T;c.5234+1G>A;c.5259delA;c.5260delG;c.5325dupA;c.5374G>T;c.5476C>T;c.5562+1G>A;c.5562+5G>C;c.5563-2A>G;c.5605G>T;c.5706_5712delCTCATCT;c.5865+2T>G;c.5866-2A>G;c.5866-1G>A;c.5914C>T;c.6011delA;c.6038delT;c.6268+2T>C;c.6334A>T;c.6429+1G>A;c.6429+1G>C;c.6429+1G>T;c.6488delA;c.6520delG;c.6573+1G>A;c.6573+1G>T;c.6617delT;c.6919_6920delTA;c.6955C>T;c.6985_6988delACTG;c.6992+5G>A;c.6993-2A>C;c.7074C>A;c.7147C>T;c.7155+1G>A;c.7279_7280delCT;c.7439+1G>A;c.7444A>T;c.7452-1G>A;c.7490_7493dupAAGA;c.7536delC;c.7572+1G>A;c.7658delC;c.7691T>C;c.7732C>T;c.7810C>T;c.7888C>T;c.7899-1G>A;c.7991delG;c.8076-1G>A;c.8155G>T;c.8169_8173delTCCAG;c.8244+1G>A;c.8245-2A>G;c.8314delA;c.8547+1G>T;c.8547+2T>C;c.8548-2A>G;c.8669dupT;c.8705delT;c.8748delA;c.8858-1G>A;c.9095dupA;c.9101_9104dupAACA;c.9211+1G>A;c.9212-2A>G;c.9212-1G>A;c.9221delA;c.9253C>T

Junctional epidermolysis bullosa (JEB) Herlitz type; JEB non-Herlitz type

Descripción enfermedad:
Junctional epidermolysis bullosa (JEB) follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the LAMA3 gene located on chromosomal region 18q11.2. The age of onset is neonatal/infancy. JEB is a group of genetic conditions that cause the skin to be very fragile and to blister easily. Blisters and skin erosions form in response to minor injury or friction, such as rubbing or scratching. Researchers classify junctional epidermolysis bullosa into two main types based on severity: Herlitz JEB and non-Herlitz JEB. Herlitz type is more severe phenotype characterized by blisters and erosions, localized to the skin and mucous membranes and often results in early death. More than 30 mutations in the LAMA3 gene have been identified in people with Herlitz JEB. Other LAMA3 gene mutations cause the milder form non-Herlitz JEB, phenotype characterized by generalized skin blistering, atrophic scarring, nail dystrophy or nail absence, and enamel hypoplasia, with extracutaneous involvement.

c.4683+2T>G;c.42G>A;c.91C>T;c.108delA;c.151dupG;c.5016C>A;c.5049delG;c.5099C>G;c.5112+1G>A;c.5112+1G>T;c.5112+2T>G;c.5113-2A>G;c.5152delT;c.5162delG;c.5197dupG;c.5205delA;c.5461+1G>A;c.5594_5597delCCCA;c.5688dupT;c.5782C>T;c.5836+2T>C;c.5980_5981delGC;c.6009delG;c.6041delA;c.6232_6233delAG;c.6266C>G;c.6318+2T>C;c.6377_6380delTAAG;c.6472G>T;c.6505delG;c.6567delC;c.6708_6711delGCTAinsCCT;c.6719-2A>G;c.6808C>T;c.6836-2A>G;c.6943A>T;c.7054A>T;c.7075C>T;c.7158+1G>A;c.7165delG;c.7343_7346delACAT;c.7459A>T;c.7489C>T;c.7654C>T;c.7677delA;c.7820delG;c.7828C>T;c.8004_8005delAG;c.8043+2T>C;c.8044-1G>T;c.8102delA;c.8177+2T>G;c.8203C>T;c.8292G>A;c.8295+2T>C;c.8436G>A;c.8436+1G>A;c.8576+1G>A;c.8576+2T>G;c.8626_8627insC;c.8708+1G>A;c.8708+1G>T;c.8708+2T>G;c.8786T>G;c.8941C>T;c.8962C>T;c.8971dupG;c.9162dupA;c.9352-1G>C;c.9400delG;c.9511+1G>A;c.9512-1G>T;c.9575delC;c.9705dupT;c.9736+1G>C

Junctional epidermolysis bullosa (JEB) Herlitz type; JEB non-Herlitz type

Descripción enfermedad:
Junctional epidermolysis bullosa (JEB) follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the LAMB3 gene located on chromosomal region 1q32.2. The age of onset is neonatal/infancy. JEB is a group of genetic conditions that cause the skin to be very fragile and to blister easily. Blisters and skin erosions form in response to minor injury or friction, such as rubbing or scratching. Researchers classify junctional epidermolysis bullosa into two main types based on severity: JEB Herlitz type and JEB non-Herlitz type. Herlitz type is more severe phenotype characterized by blisters and erosions, localized to the skin and mucous membranes and often results in early death. More than 80 mutations in the LAMB3 gene have been identified in people with JEB Herlitz type. Other LAMB3 gene mutations cause the milder form JEB non-Herlitz type, disease characterized by generalized skin blistering, atrophic scarring, nail dystrophy or nail absence, and enamel hypoplasia, with extracutaneous involvement.

c.3446_3453delGACTGGAG;c.3431C>A;c.3394dupG;c.3383-1G>A;c.3340G>T;c.3250_3251delAA;c.3228+1G>A;c.3228+1G>T;c.3119G>A;c.3052-1G>A;c.3034C>T;c.3024delT;c.2914C>T;c.2842delG;c.2806C>T;c.2701+1G>A;c.2556+1G>A;c.2362_2372delTGTGGCAACTC;c.2346delC;c.2288delG;c.2170C>T;c.2011delC;c.1978C>T;c.1977-1G>A;c.1903C>T;c.1830G>A;c.1823dupG;c.1705C>T;c.1597+1G>T;c.1587_1588delAG;c.1486-1G>A;c.1439_1443delCGTGT;c.1438_1442delCCGTG;c.1365_1366delCA;c.1357delT;c.1288+1G>A;c.1288+1G>T;c.1117C>T;c.1065_1066delTG;c.1029_1030dupTG;c.1029T>A;c.1017T>G;c.1007delA;c.978delC;c.977delA;c.943+2T>A;c.920delG;c.904delT;c.870T>A;c.823-1G>T;c.727C>T;c.629-1G>A;c.628+1delG;c.628+1G>A;c.628G>A;c.565-1G>T;c.565-2A>C;c.565-2A>G;c.561delG;c.505C>T;c.499_500delAG;c.496C>T;c.463dupT;c.430C>T;c.373-2A>G;c.372+2T>G;c.372+1G>C;c.298+2T>C;c.241C>T;c.225_226delCA;c.183+2T>C;c.124C>T;c.69_70delTG;c.29-2A>G

Junctional epidermolysis bullosa (JEB) Herlitz type; JEB non-Herlitz type

Descripción enfermedad:
Junctional epidermolysis bullosa (JEB) follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the LAMC2 gene located on chromosomal region 1q25.3. The age of onset is neonatal/infancy. JEB is a group of genetic conditions that cause the skin to be very fragile and to blister easily. Blisters and skin erosions form in response to minor injury or friction, such as rubbing or scratching. Researchers classify junctional epidermolysis bullosa into two main types based on severity: Herlitz JEB and non-Herlitz JEB. Herlitz type is more severe phenotype characterized by blisters and erosions, localized to the skin and mucous membranes and often results in early death. More than 30 mutations in the LAMC2 gene have been identified in people with Herlitz JEB. Other LAMC2 gene mutations cause the milder form non-Herlitz JEB, disease characterized by generalized skin blistering, atrophic scarring, nail dystrophy or nail absence, and enamel hypoplasia, with extracutaneous involvement.

c.80-2A>G;c.134_137delGACA;c.146_150dupATGGA;c.268+1G>A;c.283C>T;c.343C>T;c.405-1G>A;c.503+1G>C;c.504-2A>C;c.537delG;c.559_560insAA;c.640+2T>A;c.641-2A>G;c.667C>T;c.709C>T;c.733C>T;c.877_878delGG;c.953+1G>A;c.954-2A>T;c.1065C>G;c.1257delA;c.1468+1G>T;c.1659C>A;c.1714+2T>C;c.1715-1G>A;c.1715-1G>C;c.1782_1783delGC;c.1858-1G>A;c.1970_1971delAG;c.2006_2012delTTTCAGA;c.2014+1G>A;c.2137_2143delCAGAACC;c.2220+2T>G;c.2348delA;c.2389_2392delCTGC;c.2456+1G>C;c.2541_2542delCA;c.2590C>T;c.2602-1G>C;c.2755-2A>G;c.2929_2930delTC;c.3069+1G>A;c.3069+1G>C;c.3120_3121insA;c.3147dupG;c.3223_3224delCA;c.3329-2A>G;c.3357delG;c.3512dupA

Muscular dystrophy-dystroglycanopathy, type 6A and 6B

Descripción enfermedad:
Muscular dystrophy-dystroglycanopathy, type 6 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the LARGE1 gene located on chromosomal region 22q12.3. The age of onset is infantile. There are two subtypes of dystroglycanopathies related to LARGE1 gene: subtype 6A and 6B. Subtype 6A is the most severe phenotype and is associated with congenital brain and eye anomalies, cobblestone lissencephaly, profound mental retardation, and death usually in the first years of life. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease. Subtype 6B represents an intermediate phenotype with or without congenital mental retardation, white matter changes and structural brain abnormalities. The prevalence is 1:100,000-9:100,000.

c.1525G>A;c.1483T>C;c.1102C>T;c.992C>T

Pituitary hormone deficiency, combined, type 3

Descripción enfermedad:
Combined pituitary hormone deficiency type 3 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the LHX3 gene located on chromosomal region 9q34.3. The age of onset is infantile, etc/. This disease is characterized by somatolactotroph, thyrotroph and gonadotroph deficiencies, limited head and neck rotation associated with spinal abnormalities. The prevalence is <1 /1,000,000.

c.687G>A;c.644C>T;c.347A>G;c.302_303delGCinsTCCT;c.148A>T;c.111delT

Stuve-Wiedemann syndrome / Schwartz-Jampel type 2 syndrome

Descripción enfermedad:
Stüve-Wiedemann syndrome follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the LIFR gene located on chromosomal region 5p13.1. The age of onset is neonatal. This disease is characterized by small stature, congenital bowing of the long bones and campodactyly.

c.2503G>T;c.2170C>G;c.2074C>T;c.2013dupT;c.1789C>T;c.1273_1276delGTTA;c.1121+1G>A;c.1018_1022delAATTG;c.653dupT;c.503C>G;c.254delA;c.171_174delTAAC

Lysosomal acid lipase deficiency

Descripción enfermedad:
Deficiency of lysosomal acid lipase causes 2 distinct phenotypes in humans: Wolman disease and cholesteryl ester storage disease (CESD). Wolman disease is an early-onset fulminant disorder of infancy with massive infiltration of the liver, spleen, and other organs by macrophages filled with cholesteryl esters and triglycerides. Death occurs early in life. Wolman disease is very rare, with an incidence of less than one in 100,000 live births. CESD is a milder, later-onset disorder with primary hepatic involvement by macrophages engorged with cholesteryl esters. This slowly progressive visceral disease has a very wide spectrum of involvement ranging from early onset with severe cirrhosis to later onset of more slowly progressive hepatic disease with survival into adulthood (Du et al., 2001).

c.894+2T>C;c.894G>A;c.894G>C;c.892C>T;c.822+1G>A;c.822+1G>C;c.796G>T;c.684delT;c.676-2A>G;c.656T>G;c.599T>C;c.594dupT;c.482delA;c.428+1G>A;c.419G>A;c.397_398delTC;c.398delC;c.350_351insCC;c.260G>T;c.253C>T;c.193C>T;c.129C>G;c.111+2T>G

Deafness, autosomal recessive type 77

Descripción enfermedad:
Autosomal recessive nonsyndromic sensorineural deafness type 77 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the LOXHD1 gene located on chromosomal region 18q21.1. The age of onset is infantile. This disease is characterized by mild-to-profound sensorineural hearing impairment with no associated visible abnormalities of the external ear or any related medical problems.

c.5944C>T;c.5894dupG;c.4989G>A;c.4741-1G>A;c.4714C>T;c.4524_4525delAG;c.4480C>T;c.4376-2A>G;c.4099G>T;c.4096-1G>C;c.3924C>A;c.3169C>T;c.3148G>T;c.3061+1G>A;c.3061+1G>T;c.2870C>A;c.2696G>C;c.2598+1G>C;c.2497C>T;c.2303delG;c.2244+2T>G;c.2008C>T;c.894T>G;c.746G>A;c.512-1G>A;c.457_461dupCGCCA;c.442A>T

Leigh syndrome, French-Canadian type

Descripción enfermedad:
French-Canadian type Leigh syndrome follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the LRPPRC gene located on chromosomal region 2p21. The age of onset is infantile. This disease is characterized by chronic metabolic acidosis, hypotonia, facial dysmorphism and delayed development. The prevalence is 1:2,000 newborn.

c.4128+2T>G;c.4128+1G>A;c.3963C>A;c.3952G>T;c.3900+1G>C;c.3830_3839delGTGGTGCAATinsAG;c.3673_3676delGTAA;c.3286delC;c.3147dupA;c.3045G>A;c.3003_3006delAGAG;c.2984T>G;c.2755C>T;c.2737-1G>T;c.2736+1G>T;c.2545_2558delTATGAAAAGTATAA;c.2505-1G>T;c.2450T>A;c.2296+1G>A;c.2080-1G>C;c.1970_1971delTG;c.1920+1G>T;c.1865_1868delTCTA;c.1842+2T>A;c.1792C>T;c.1723C>T;c.1649_1649+1delGGinsTTT;c.1589C>A;c.1577C>A;c.1261+2T>C;c.1091C>G;c.1061C>T;c.864+2T>C;c.650+1G>C;c.601C>T;c.600C>A;c.589C>T;c.469+1G>A;c.251_254delATTG;c.254G>A

Chediak-Higashi syndrome

Descripción enfermedad:
Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by hypopigmentation, severe immunologic deficiency, a bleeding tendency, neurologic abnormalities, abnormal intracellular transport to and from the lysosome, and giant inclusion bodies in a variety of cell types. Most patients die at an early age unless they receive an allogeneic hematopoietic stem cell transplant.

c.10395delA;c.10345C>T;c.10127A>G;c.9893delT;c.9590delA;c.9228_9229insTTCTTTCAGT;c.8802-2A>G;c.8583G>A;c.8281A>T;c.7982C>G;c.7555delT;c.7159C>T;c.7060_7066delCTATTAG;c.6694G>T;c.6078C>A;c.5956C>T;c.5541_5542delAA;c.5506C>T;c.5317delA;c.5061T>A;c.4688+1G>A;c.4274delT;c.4052C>G;c.3944dupC;c.3622C>T;c.3434dupA;c.3310C>T;c.3085C>T;c.3073_3074delAA;c.2623delT;c.2454delA;c.2413delG;c.2413G>T;c.1902dupA;c.1540C>T;c.1467delG;c.925C>T;c.772T>C;c.148C>T;c.118dupG

Mannosidosis, alpha-, types I and II

Descripción enfermedad:
Alpha-mannosidosis follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the MAN2B1 gene located on chromosomal region 19p13.2. The age of onset is infantile. This disease is characterized by immunodeficiency, facial and skeletal abnormalities, hearing impairment and intellectual disability. The prevalence is 1:1,000,000-9:1,000,000.

c.2921_2922delCA;c.2922delA;c.2820+1G>A;c.2802dupC;c.2696C>A;c.2686_2687delCTinsG;c.2669C>G;c.2665-1G>C;c.2664+1G>A;c.2436+2T>C;c.2436+1G>A;c.2426T>C;c.2402dupG;c.2398G>A;c.2368C>T;c.2356-2A>G;c.2299C>T;c.2278C>T;c.2268-1G>C;c.2248C>T;c.2165+1G>A;c.2119C>T;c.2114delC;c.2047-1G>A;c.2046+2T>A;c.2046+1G>A;c.2046+1G>T;c.2013delT;c.1929G>A;c.1929-1G>T;c.1915C>T;c.1851delT;c.1831-2A>G;c.1830+1G>C;c.1774_1783delGCACCACAGC;c.1780C>T;c.1687G>T;c.1645-1G>A;c.1645-2A>T;c.1528-1G>T;c.1527+1G>C;c.1468_1472delTTCAC;c.1390C>T;c.1383C>A;c.1383C>G;c.1310-1G>A;c.1309+1G>T;c.1163G>A;c.1109G>A;c.1026+2T>C;c.764-1G>C;c.446delA;c.422delA;c.418C>T;c.384G>A;c.277C>T;c.231G>A;c.159+2T>C;c.159+1G>A;c.1A>G

3-Methylcrotonyl-CoA carboxylase type 2, deficiency

Descripción enfermedad:
3-methylcrotonyl-CoA carboxylase deficiency type 2 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the MCCC2 gene located on chromosomal region 5q13.2. The age of onset is neonatal. This disease is characterized by a highly variable clinical picture ranging from neonatal onset with severe neurological involvement to asymptomatic adults. The prevalence is 1:75,000 newborn.

c.142C>T;c.214C>T;c.295G>C;c.302C>A;c.380C>G;c.449_450delTG;c.463C>T;c.464G>A;c.499T>C;c.517dupT;c.538C>T;c.569A>G;c.641delG;c.652G>A;c.735dupC;c.838G>T;c.929C>G;c.994C>T;c.1015G>A;c.1065A>T;c.1072+1G>A;c.1081C>T;c.1216+2T>C;c.1574+1G>A;c.1577dupT;c.1580G>A

Mucolipidosis type 4

Descripción enfermedad:
Mucolipidosis type 4 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the MCOLN1 gene located on chromosomal region 19p13.2. The age of onset is infantile. This disease is characterized by psychomotor retardation and visual abnormalities including corneal clouding, retinal degeneration, or strabismus. The prevalence is 1:40,000.

c.31+1G>A;c.32-2A>G;c.38_41dupAGCG;c.54dupC;c.235C>T;c.302_303delTC;c.304C>T;c.378C>G;c.405+1G>A;c.406-2A>G;c.473_474delCC;c.514C>T;c.571+2T>C;c.615dupC;c.681-2A>G;c.777+1G>C;c.855_856insA;c.964C>T;c.984+1G>A;c.1047dupA;c.1084G>T;c.1134+2T>C;c.1135-2A>G;c.1135-1G>A;c.1135-1G>C;c.1207C>T;c.1210dupT;c.1340T>C;c.1388G>A;c.1395C>G;c.1406A>G;c.1453_1463dupGGCCGCAGCAG;c.1447C>T;c.1615delG

Encephalopathy, neonatal severe

Descripción enfermedad:
Encephalopathy, neonatal severe follows an X -linked pattern of inheritance and is caused by pathogenic variants in the MECP2 gene located on chromosomal region Xq28. The age of onset is neonatal. This neurological disorder primarily affects males and causes brain dysfunction (encephalopathy). Affected males have microcephaly, poor muscle tone (hypotonia), movement disorders, rigidity, and seizures. Individuals with MECP2-related severe neonatal encephalopathy have severe to profound intellectual disability. Genetic heterogeneity: Many of the mutations causing male's phenotype also cause Rett syndrome, a severe neurodevelopmental disorder that almost always occurs in females. Most severe neonatal encephalopathy cases are surviving male sibs of patients with Rett syndrome. Males with non-Rett syndrome mutations in the MECP2 gene can demonstrate a wide variety of phenotypes. Note: other conditions are also associated to the MECP2 gene, like MECP2 duplication syndrome, a condition characterized by intellectual disability, delayed development, and seizures. It is caused by a duplication of the MECP2 gene and surrounding DNA; this duplication is not tested in the CGT analysis.

c.1491_1492dupTA;c.1486_1489delAGAG;c.1451_1452delAG;c.1444_1447delAACAinsTG;c.1400_1401insC;c.1399G>T;c.1393C>T;c.1366_1378delGCCACGGCCGCAG;c.1356dupT;c.1344_1345delTC;c.1252C>T;c.1238dupG;c.1233dupC;c.1230_1231insT;c.1226dupA;c.1225G>T;c.1194_1203delGCCCCCACCT;c.1196_1202delCCCCACC;c.1200delA;c.1198_1199delCC;c.1199dupC;c.1195_1196delCCinsT;c.1192_1193dupCT;c.1188_1191delACCC;c.1171_1178delCCCGTGCC;c.1163_1173delCAAAGGCCCCC;c.1173dupC;c.1154C>G;c.1122delC;c.1123A>T;c.1115C>A;c.1065delG;c.1030_1034delAGCGG;c.1025_1030delAGAAGAinsGCATCTTCTCCTCTTT;c.1001C>T;c.1000C>T;c.953G>A;c.952C>T;c.951G>T;c.946A>C;c.942delC;c.934_940delGTACTCC;c.941C>G;c.934_937delGTAC;c.934delG;c.925C>T;c.916_920delCGATC;c.919delT;c.905_916delAGTCTTCTATCCinsCACA;c.916C>T;c.910_911insA;c.905dupA;c.901_902delAA;c.900dupG;c.901A>T;c.892_895delAAAG;c.891_895delGAAAGinsAAAAAAAAGACT;c.890dupA;c.866delC;c.855delG;c.848_854delAGCCGGG;c.846_849delAAAG;c.844delC;c.844C>T;c.842delG;c.835A>T;c.828_829delTC;c.820C>T;c.802_815dupAAAGCTGAGGCCGA;c.802A>T;c.792_799dupCAGGAAGC;c.799C>T;c.792_795delCAGG;c.796A>T;c.791delG;c.791dupG;c.788_789dupCC;c.789delC;c.789dupC;c.784_789delCGCCCCinsGGCCG;c.786delCinsTCAGGAAGCTT;c.784_785insT;c.784dupC;c.772_779delATGGTGATinsGTG;c.775delG;c.766C>T;c.751delG;c.746delG;c.746dupG;c.732delC;c.731delG;c.731dupG;c.714delT;c.713_714insA;c.710C>G;c.710C>T;c.690_693delGAAG;c.687_688delTG;c.658C>T;c.656dupT;c.653delG;c.649G>T;c.647_648delCAinsAG;c.647C>G;c.644_645insA;c.637dupG;c.634A>T;c.628A>T;c.610A>T;c.605G>A;c.603dupA;c.602delG;c.602dupG;c.592A>T;c.590delG;c.579_580delTC;c.574A>T;c.567delA;c.565A>T;c.559A>T;c.544C>T;c.538C>T;c.535C>T;c.531delC;c.524_525delGG;c.519delG;c.520A>G;c.516_517delTG;c.516delT;c.511delG;c.509C>T;c.508A>G;c.504C>A;c.504C>G;c.500T>C;c.490C>G;c.487delG;c.488A>G;c.475delG;c.467delA;c.466A>T;c.458dupA;c.459C>G;c.456delG;c.455C>T;c.449T>A;c.447delG;c.446A>G;c.439A>G;c.437C>G;c.437C>T;c.434G>A;c.414-3_419delCAGTCCCCA;c.418C>T;c.416C>T;c.414-2A>C;c.414-2A>G;c.414-2A>T;c.413+1G>A;c.413+1G>T;c.411delC;c.412A>G;c.400G>A;c.381delC;c.368G>A;c.362dupA;c.361A>G;c.347_359delGGACACGGAAGCT;c.354_357dupGAAG;c.353G>A;c.351dupA;c.352C>T;c.347G>A;c.338C>A;c.338C>G;c.338C>T;c.337C>T;c.334C>G;c.311delG;c.311dupG;c.310G>T;c.294_295delCA;c.279dupC;c.265_274delGCTTCTGCCT;c.269delC;c.251_252insT;c.251dupC;c.239C>G;c.237delG;c.230C>G;c.225_226delGA;c.203_204delCC;c.182C>A;c.182C>G;c.176dupA;c.162dupG;c.155_156delAG;c.153dupA;c.143_149delAAGAAGA;c.144_147delAGAA;c.143_144delAA;c.136_139delGATA;c.127delG;c.112delC;c.100A>T;c.83_93delAGGACCTCCAG;c.92dupA;c.91C>T;c.86dupA;c.82C>T;c.71_78dupAGTCAGAA;c.64G>T;c.63-2A>G;c.26+2T>A;c.62+2T>G;c.62+1G>A;c.59_60delGA;c.47_57delGCGAGGAGGAG;c.48_55delCGAGGAGG;c.48_55dupCGAGGAGG;c.30delCinsGA;c.23_27dupCGCCG;c.1A>G;c.1A>T

Familial Mediterranean fever

Descripción enfermedad:
Familial Mediterranean fever follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the MEFV gene located on chromosomal region 16p13.3. The age of onset is infantile or adult (before the age of 30). This disease is characterized by recurrent short episodes of fever and serositis resulting in pain in the abdomen, chest, joints and muscles. In rare cases, this condition appears to be inherited in an autosomal dominant pattern. The prevalence is 1:10,000-5:10,000.

c.2282G>A;c.2230G>T;c.2177T>C;c.2081_2083delTGA;c.2084A>G;c.2082G>A;c.2080A>G;c.2076_2078delAAT;c.2064C>G;c.2060G>A;c.2040G>A;c.2040G>C;c.1958G>A;c.1894G>A;c.1759+1G>A;c.1437C>G;c.1141C>T;c.826G>T;c.656dupG;c.501G>C;c.277+1G>T;c.163dupA

Ceroid lipofuscinosis, neuronal, type 7

Descripción enfermedad:
Neuronal ceroid lipofuscinosis type 7 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the MFSD8 gene located on chromosomal region 4q28.2. The age of onset is late infantile. This disease is characterized by decline of mental and motor capacities, epilepsy, and vision loss through retinal degeneration. The prevalence is 0.56:100,000-3.9:100,000.

c.1525_1526delCT;c.1444C>T;c.1361T>C;c.1351-2A>G;c.1286G>A;c.1235C>T;c.1141G>T;c.1090delA;c.1061dupT;c.999-2A>G;c.998+1G>A;c.929G>A;c.894T>G;c.881C>A;c.863+1G>A;c.754+2T>A;c.754+1G>T;c.599G>A;c.554-2A>T;c.553+1G>A;c.525T>A;c.440-2A>T;c.416G>A;c.362A>G;c.217dupA;c.64G>T

Bardet-Biedl syndrome type 13; Meckel syndrome, type 1

Descripción enfermedad:
Bardet-Biedl syndrome type 13 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the MKS1 gene located on chromosomal region 17q22. The age of onset is antenatal or infacy. This disease is characterized by a combination of clinical signs: obesity, pigmentary retinopathy, post-axial polydactyly, polycystic kidneys, hypogenitalism, and learning disabilities, many of which appear several years after disease onset. Clinical expression is variable but most patients manifest the majority of clinical signs during the disease course. Meckel syndrome, type 1 is a disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly.

c.1506-2A>T;c.1505+1G>T;c.1445dupC;c.1408-2A>G;c.841_844dupGGCA;c.799-2A>G;c.1407+2delT;c.1394delC;c.1166-2A>C;c.1166-2A>G;c.1115_1117delCCT;c.1112_1114delTCT;c.1066C>T;c.1048C>T;c.1025-2A>C;c.1024+1G>A;c.858+1G>A;c.844C>T;c.829G>T;c.767_768insC;c.645-2A>T;c.515+2T>G;c.515+1G>A;c.508C>T;c.472C>T;c.424C>T;c.417+1G>A;c.392_393delCT;c.381delC;c.367dupC;c.261+2T>A;c.190+2T>C;c.184_190delACTGCCA;c.80+2T>C;c.51_55dupCCGGG

Megalencephalic leukoencephalopathy with subcortical cysts

Descripción enfermedad:
Megalencephalic leukoencephalopathy with subcortical cysts follows an autosomal recessive patternof inheritance and is caused by pathogenic variants in the MLC1 gene located on chromosomal region 22q13.33. The age of onset is infantile. This disease is characterized by ataxia followed by progressive signs of pyramidal tract involvement and mental deterioration.

c.1059+1G>A;c.973C>T;c.895-1G>C;c.714+1G>A;c.624_625delTG;c.594_597delCTCA;c.525+1G>A;c.449_455delTCCTGCT;c.448delC;c.424-2A>C;c.423C>A;c.422A>G;c.324delT;c.321+1G>A;c.321+1G>T;c.278C>T;c.274C>T;c.271_272delAT;c.223delG;c.206C>T;c.178-10T>A;c.176G>A;c.136delT;c.135dupC;c.83dupA;c.67C>T;c.42delG;c.33dupC

Methylmalonic aciduria, vitamin B12-responsive

Descripción enfermedad:
Vitamin B12-responsive methylmalonic acidemia type cblA follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the MMAA gene located on chromosomal region 4q31.21. The age of onset is early infantile. This disease is characterized by developmentally delayed with other features that include hypotonia, seizures, hypoglycaemia, metabolic acidosis, cardiomyopathy and diarrhoea. The prevalence is <1:1,000,000.

c.15_16delAC;c.64C>T;c.72C>A;c.161G>A;c.202C>T;c.267_268delTT;c.266T>C;c.283C>T;c.358C>T;c.387C>A;c.397C>T;c.411_414delTAAA;c.433C>T;c.439+1G>A;c.441dupA;c.450dupG;c.455delC;c.503delC;c.527_528delTG;c.551dupG;c.562G>C;c.562+1G>A;c.562+1G>T;c.586C>T;c.593_596delCTGA;c.594dupT;c.620A>G;c.650T>A;c.651dupA;c.653G>A;c.733+1G>A;c.742C>T;c.812_813dupAG;c.811G>T;c.820-1G>A;c.970-2A>T;c.988C>T;c.1034delT;c.1075C>T;c.1076G>A;c.1084C>T

Methylmalonic aciduria, vitamin B12-responsive, type cblB

Descripción enfermedad:
Vitamin B12-responsive methylmalonic acidemia type cbl B follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the MMAB gene located on chromosomal region 12q24.31. The age of onset is early infantile. This disease is characterized by developmentally delayed with other features that include hypotonia, seizures, hypoglycaemia, metabolic acidosis, cardiomyopathy and diarrhoea. The prevalence is <1:1,000,000.

c.700C>T;c.585-2A>C;c.584G>A;c.563_577dupTGTGCCGCCGGGCCG;c.573_577delGGCCG;c.570_572dupCCG;c.572G>A;c.571C>T;c.569G>A;c.568C>G;c.568C>T;c.563T>G;c.556C>T;c.454G>T;c.349-1G>C;c.291-1G>A;c.290G>A;c.287T>C;c.220G>T;c.197-1G>A;c.197-1G>T;c.12C>A

Methylmalonic aciduria and homocystinuria, cblC type

Descripción enfermedad:
Vitamin B12-responsive methylmalonic acidemia type cbl B follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the MMAB gene located on chromosomal region 12q24.31. The age of onset is early infantile. This disease is characterized by developmentally delayed with other features that include hypotonia, seizures, hypoglycaemia, metabolic acidosis, cardiomyopathy and diarrhoea. The prevalence is <1:1,000,000.

c.1A>G;c.3G>A;c.81+2T>G;c.82-1G>A;c.90G>A;c.217C>T;c.271dupA;c.273_276delAGAG;c.285dupA;c.292C>T;c.310_313delGACT;c.315C>G;c.328_331delAACC;c.331C>T;c.347T>C;c.352delC;c.388_390delTAC;c.389A>G;c.391C>T;c.394C>T;c.398_399delAA;c.420G>A;c.427C>T;c.445_446delTG;c.440G>A;c.440G>C;c.457C>T;c.464G>A;c.471G>A;c.481C>T;c.482G>A;c.500delC;c.507_519delAGAGGTGCCAGAT;c.547_548delGT;c.565delC;c.567dupT;c.608G>A;c.609G>A;c.615C>A;c.615C>G;c.616C>T;c.619dupG;c.658_660delAAG;c.666C>A;c.688C>T

Homocystinuria, cblD type, variant 1

Descripción enfermedad:
Homocystinuria, cblD type, variant 1 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the MMADHC gene located on chromosomal region 2q23.2. The age of onset is variable (infantile to adult). This disease is characterized by developmental delay, severe learning difficulties, seizures, movement and gait abnormalities, behavioral problems and signs of megaloblastic anemia (pallor, fatigue, anorexia). The prevalence is 1:50,000-1:80,000.

c.795dupT;c.776T>C;c.748C>T;c.746A>G;c.545C>A;c.478+1G>T;c.472C>T;c.455dupC;c.419dupA;c.228dupG;c.160C>T;c.133dupG;c.57_64delCTCTTTAG;c.60_61insAT

Methylmalonic aciduria, mut(0) type

Descripción enfermedad:
Methylmalonic acidemia follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the MUT gene located on chromosomal region 6p12.3. The age of onset is very early infantile. This disease is characterized by recurrent ketoacidotic comas or transient vomiting, dehydration, hypotonia and intellectual deficit, which does not respond to administration of vitamin B12.

c.2200C>T;c.2193_2196dupTGCC;c.2194_2197delGCCGinsTGGAA;c.2179C>T;c.2150G>T;c.2106delA;c.2107G>C;c.2099T>A;c.2080C>T;c.2078delG;c.2054T>G;c.1975C>T;c.1962_1963delTC;c.1957-2A>G;c.1956+2T>C;c.1946delC;c.1924G>C;c.1889G>A;c.1885dupA;c.1885A>G;c.1880A>G;c.1874A>G;c.1871A>G;c.1867G>A;c.1867G>C;c.1853T>C;c.1777G>T;c.1741C>T;c.1718T>C;c.1677-1G>A;c.1677-1G>C;c.1663G>A;c.1658delT;c.1655C>T;c.1630_1631delGGinsTA;c.1599T>A;c.1560+1G>T;c.1553T>C;c.1531C>T;c.1489G>T;c.1481T>A;c.1445-2A>G;c.1420C>T;c.1399C>T;c.1351G>T;c.1332+1delG;c.1287C>G;c.1280G>A;c.1277G>A;c.1271C>T;c.1207C>T;c.1196_1197delTG;c.1181dupT;c.1181T>A;c.1164T>A;c.1130C>A;c.1126_1127delGC;c.1108A>C;c.1106G>A;c.1105C>T;c.1097A>G;c.1084-1G>A;c.1084-1G>C;c.1084-2A>G;c.1084-10A>G;c.1083+2T>A;c.1083+1G>A;c.1065_1068dupATGG;c.1025C>A;c.1022dupA;c.1007delT;c.982C>T;c.977G>A;c.976A>G;c.974G>A;c.935G>T;c.927G>A;c.914T>C;c.851G>A;c.850G>A;c.850G>T;c.842T>C;c.754-2A>G;c.753+2T>A;c.729_730insTT;c.692dupA;c.693C>G;c.691T>A;c.689C>G;c.682C>T;c.671_678dupAATTTATG;c.670G>T;c.655A>T;c.643G>A;c.643G>T;c.630delA;c.607G>A;c.572C>A;c.566A>T;c.560C>G;c.521T>C;c.467A>T;c.454C>T;c.415G>A;c.410C>G;c.397G>A;c.394C>T;c.385+2T>C;c.372_374dupGGA;c.360dupT;c.349G>T;c.330T>G;c.329A>G;c.323G>A;c.322C>T;c.312delC;c.313T>C;c.299A>G;c.284C>G;c.280G>A;c.278G>A;c.160A>T;c.129G>A;c.91C>T;c.88C>T;c.55dupG;c.52C>T;c.30dupA;c.29dupT;c.19C>T;c.2T>C;c.-39-1G>A

Congenital disorder of glycosylation, type 2B

Descripción enfermedad:
Congenital disorder of glycosylation, type 2B (CDG2B) is characterized by marked generalized hypotonia and hypomotility of the neonate, dysmorphic features, including a prominent occiput, short palpebral fissures, retrognathia, high arched palate, generalized edema, and hypoplastic genitalia.

c.1457G>C;c.370C>T

Congenital disorder of glycosylation, type 1b

Descripción enfermedad:
Congenital disorder of glycosylation type 1b follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the MPI gene located on chromosomal region 15q24.1. The age of onset is infantile. This disease is characterized by hepatic-intestinal manifestations (diarrhoea, vomiting, and hepatomegaly associated with hepatic fibrosis).

c.-1_3delCATG;c.120delC;c.145-1G>A;c.166dupC;c.305C>T;c.345+1G>A;c.413T>C;c.488-1G>A;c.488-1G>C;c.629delT;c.652A>T;c.656G>A;c.727C>T;c.740delG;c.802_803delAT;c.844+1G>A;c.884G>A;c.1016_1019delACCC;c.1253G>A

Thrombocytopenia, congenital amegakaryocytic

Descripción enfermedad:
Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare disorder expressed in infancy and characterized by isolated thrombocytopenia and megakaryocytopenia with no physical anomalies (Muraoka et al., 1997). King et al. (2005) proposed a new classification of CAMT based on the course and outcome of the disease, as exemplified by 20 patients: CAMT type 1 (11 patients) was characterized by early onset of severe pancytopenia, decreased bone marrow activity, and very low platelet counts. CAMT type 2 (9 patients) was somewhat milder and characterized by transient increases of platelet counts up to nearly normal values during the first year of life and an onset of bone marrow failure at age 3 or later. Also, a family with thrombocythemia was reported by Ding et al. (2004) with an autosomal dominant inheritance pattern due to a heterozygous mutation in the MPL gene.

c.79+2T>A;c.127C>T;c.235_236delCT;c.305G>C;c.378delT;c.391+5G>C;c.556C>T;c.769C>T;c.823C>A;c.972delC;c.1303T>A;c.1468+2T>C;c.1473G>A;c.1513A>T;c.1514G>A;c.1543_1544delTGinsAA;c.1904C>T

Mitochondrial DNA depletion syndrome type 6 (hepatocerebral); Charcot-Marie-Tooth disease, axonal, type 2EE

Descripción enfermedad:
Mitochondrial DNA depletion syndrome type 6 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the MPV17 gene located on chromosomal region 2p23.3. The age of onset is infantile. It is a disease due to mitochondrial dysfunction. It is characterized by infantile onset of progressive liver failure, often leading to death in the first year of life, peripheral neuropathy, corneal scarring, acral ulceration and osteomyelitis leading to autoamputation, cerebral leukoencephalopathy, failure to thrive, and recurrent metabolic acidosis with intercurrent infections. Charcot-Marie-Tooth disease type 2EE (CMT2EE) is an autosomal recessive sensorimotor peripheral axonal neuropathy with onset in the first or second decades of life. The disorder primarily affects the lower limbs and is slowly progressive, sometimes resulting in loss of ambulation, with later onset of upper limb involvement. There is significant distal muscle weakness and atrophy, usually with foot or hand deformities. Skeletal muscle biopsy shows findings of disturbed mitochondrial maintenance. Cognition is unaffected, and chronic liver disease is absent (summary by Baumann et al., 2019).

c.498C>A;c.462-2A>C;c.461+2T>C;c.461G>T;c.409-1G>C;c.408+1G>A;c.376-1G>A;c.376-2A>C;c.370C>T;c.359G>A;c.297T>A;c.293delC;c.293C>T;c.284dupG;c.263_265delAGA;c.206G>A;c.191C>G;c.186+2T>C;c.149G>A;c.148C>T;c.135delA;c.106C>T;c.70G>T;c.22dupC

Myotubular myopathy, X-linked

Descripción enfermedad:
X-linked centronuclear myopathy follows an X-linked pattern of inheritance and is caused by pathogenic variants in the MTM1 gene located on chromosomal region Xq28. The age of onset is infantile, etc/. This disease is characterized by severe phenotype in males presenting at birth with marked weakness, hypotonia and respiratory failure. The incidence is 1/50,000 newborn man.

c.2T>G;c.3G>A;c.19delT;c.49G>T;c.63+1G>A;c.64-1G>A;c.70C>T;c.85C>T;c.96dupT;c.109C>T;c.130dupA;c.141_144delAGAA;c.142_143delGA;c.145G>A;c.145G>T;c.153_156delCATA;c.154delA;c.205C>G;c.205C>T;c.208C>T;c.226G>T;c.231+1G>A;c.231+2T>G;c.232-2A>C;c.232-1G>A;c.252delT;c.260T>C;c.342_342+4delAGTAA;c.340A>T;c.342+1G>A;c.343-2A>G;c.397_398delAT;c.402delT;c.419dupA;c.420C>G;c.431delT;c.444+1G>A;c.461T>G;c.465delT;c.469delG;c.469G>A;c.514G>T;c.528+1G>T;c.529-2A>G;c.535C>T;c.539_545delATCACCA;c.549dupG;c.549G>A;c.550A>G;c.557C>T;c.567_569delTAA;c.566A>G;c.591_594delTTAC;c.593dupA;c.595_599delCCTGC;c.605delT;c.611T>G;c.614C>T;c.629A>G;c.637C>T;c.664C>T;c.670C>T;c.676C>A;c.678+1G>A;c.679-1G>A;c.679G>A;c.683T>C;c.721C>T;c.743G>T;c.757C>T;c.779A>C;c.780T>A;c.791T>G;c.808_811delCAAA;c.867_867+1dupGG;c.867+1G>A;c.888_889delAA;c.912delC;c.949dupA;c.958T>C;c.961_962delTT;c.969delA;c.969dupA;c.1015dupT;c.1036T>C;c.1040T>G;c.1088_1089delAA;c.1089dupA;c.1120C>G;c.1132G>A;c.1136G>A;c.1137G>A;c.1139A>T;c.1160C>A;c.1180G>C;c.1190A>G;c.1191T>G;c.1204G>A;c.1205G>C;c.1210G>A;c.1227_1228delAGinsT;c.1232G>A;c.1244G>A;c.1260+1G>A;c.1261-10A>G;c.1261-1G>C;c.1261C>T;c.1262G>A;c.1283delA;c.1283_1286delACCA;c.1306_1310dupCCTAT;c.1307delC;c.1307C>T;c.1325T>A;c.1328A>C;c.1337G>A;c.1349_1353+4delAACAGGTAA;c.1353+1G>A;c.1353+2T>C;c.1354-1G>A;c.1357_1358delCC;c.1376A>T;c.1378G>T;c.1388T>C;c.1388T>G;c.1415_1416delGT;c.1420C>T;c.1427G>T;c.1433T>C;c.1456C>T;c.1464_1467delACAG;c.1467+1G>A;c.1467+1G>T;c.1467+2T>A;c.1490C>A;c.1495T>C;c.1509delC;c.1558C>T;c.1611C>A;c.1644+3_1644+6delAAGT;c.1644+1G>T;c.1792delC

Homocystinuria-megaloblastic anemia, cblG complementation type

Descripción enfermedad:
Homocystinuria and megaloblastic anemia is an autosomal recessive inborn error of metabolism resulting from defects in the cobalamin (vitamin B12)-dependent pathway that converts homocysteine to methionine, which is catalyzed by methionine synthase. Clinical features are somewhat variable, but include delayed psychomotor development, megaloblastic anemia, homocystinuria, and hypomethioninemia, all of which respond to cobalamin supplementation. Methylmalonic aciduria is not present. Two complementation groups have been described based on fibroblast studies: CblE (236270) and CblG (Watkins and Rosenblatt, 1988). Most patients present in early infancy, but some patients with CblG have shown later onset (Outteryck et al., 2012). Cells from patients with CblE fail to incorporate methyltetrahydrofolate into methionine in whole cells, but cell extracts show normal methionine synthase activity in the presence of a reducing agent. Cells from patients with CblG have defects in the methionine synthase enzyme under both conditions (Leclerc et al., 1996).CblE is caused by mutation in the MTRR gene (602568). Watkins and Rosenblatt (1989) commented on the clinical and biochemical heterogeneity in patients with cblE and cblG.

c.1228G>C;c.1753C>T;c.2003delA;c.2114_2115delTC;c.2669_2670delTG;c.3380dupA;c.3518C>T;c.3613G>T

Homocystinuria-megaloblastic anemia, cbl E type

Descripción enfermedad:
Homocystinuria and megaloblastic anemia is an autosomal recessive inborn error of metabolism resulting from defects in the cobalamin (vitamin B12)-dependent pathway that converts homocysteine to methionine, which is catalyzed by methionine synthase (MTR; 156570). Clinical features are somewhat variable, but include delayed psychomotor development, hypotonia, megaloblastic anemia, homocystinuria, and hypomethioninemia, all of which respond to cobalamin supplementation. Methylmalonic aciduria is not present. Two complementation groups have been described based on fibroblast studies: CblE and CblG (250940) (Watkins and Rosenblatt, 1988). Cells from patients with CblE fail to incorporate methyltetrahydrofolate into methionine in whole cells, but cell extracts show normal methionine synthase activity in the presence of a reducing agent. Cells from patients with CblG have defects in the methionine synthase enzyme under both conditions (Leclerc et al., 1996).CblG is caused by mutation in the MTR gene.

c.1442C>T;c.1460T>G;c.1540G>A;c.1654C>T

Abetalipoproteinemia

Descripción enfermedad:
Abetalipoproteinemia follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the MTTP gene located on chromosomal region 4q23. The age of onset is infantile. This disease is characterized by growth delay, malabsorption, hepatomegaly, and neurological and neuromuscular manifestations. The prevalence is <1:1,000,000.

c.789_790delCA;c.1639-2A>G;c.1700G>A;c.1850G>T;c.1864C>T;c.1948+1G>A;c.2112delC;c.2293delT;c.2674G>T

Usher syndrome, type 1B; Deafness, autosomal recessive, type 2

Descripción enfermedad:
Usher syndrome type 1B follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the MYO7A gene located on chromosomal region 11q13.5. The age of onset is infantile. This disease is characterized by congenital, bilateral, profound sensorineural hearing loss, vestibular areflexia, and adolescent-onset retinitis pigmentosa. The prevalence is 1:100,000-9:100,000. Mutation in the MYO7A gene can also cause deafness autosomal recesive, type 2 which involves changes in both the inner ear and the middle ear. This combination is called mixed hearing loss.

c.3G>A;c.18+2T>A;c.19-2A>G;c.22dupG;c.19-1G>A;c.47T>A;c.52C>T;c.73G>A;c.93C>A;c.133-2A>C;c.133-2A>G;c.133G>T;c.137_138dupAC;c.141G>A;c.223delG;c.224dupA;c.285+1G>C;c.285+2T>C;c.285+2T>G;c.287C>T;c.324C>A;c.338_348dupTCTACTCGCCA;c.397dupC;c.397C>T;c.401T>A;c.448C>T;c.458G>A;c.470+1G>A;c.471-1G>A;c.487G>A;c.494C>T;c.496delG;c.565_566delGT;c.582delC;c.620A>G;c.634C>T;c.635G>A;c.640G>A;c.652G>A;c.689C>T;c.700C>T;c.721C>T;c.722G>A;c.731G>C;c.973_976delATCC;c.999T>G;c.1097T>C;c.1184G>A;c.1200+1G>A;c.1258A>T;c.1343+1G>A;c.1344-2A>G;c.1344-1G>A;c.1373A>T;c.1555-8C>G;c.1556G>A;c.1563delC;c.1591C>T;c.1623dupC;c.1667G>T;c.1690+1G>A;c.1691-2A>G;c.1797G>A;c.1798-1G>A;c.1820C>A;c.1845delG;c.1884C>A;c.1900C>T;c.1935+1G>C;c.1952_1953insAG;c.1952T>C;c.1963C>T;c.1976C>A;c.1977delA;c.1996C>T;c.2005C>T;c.2094+1G>A;c.2094+1G>C;c.2115C>A;c.2172delC;c.2187+1G>A;c.2241_2242delAG;c.2283-2_2293delAGGTCTAACTTTC;c.2283-1G>T;c.2307delC;c.2323C>T;c.2361C>A;c.2461C>T;c.2476G>A;c.2878G>T;c.2905-1G>A;c.3064_3067delCTCA;c.3262C>T;c.3298G>T;c.3310A>T;c.3327delC;c.3476G>T;c.3503G>A;c.3504-2A>G;c.3504-1G>C;c.3508G>A;c.3532delC;c.3543_3544dupCA;c.3564_3571delTGCCCGGGinsA;c.3576G>A;c.3594C>A;c.3596dupT;c.3628A>T;c.3631-1G>C;c.3696_3706delAAGGACCTTTG;c.3719G>A;c.3724C>T;c.3728dupC;c.3728C>G;c.3728C>T;c.3764delA;c.3815_3822delTGCTGACG;c.3892G>A;c.3924+1G>C;c.4006C>T;c.4024delT;c.4065delC;c.4074delC;c.4108_4111delCAGG;c.4117C>T;c.4153-2A>G;c.4184dupA;c.4254delC;c.4293G>A;c.4297delC;c.4442-2A>C;c.4442-1G>C;c.4502_4503delTG;c.4544_4551delAGATCATGinsCA;c.4555delG;c.4569-1G>A;c.4659_4660delCT;c.4821T>A;c.4838delA;c.4894delC;c.4919delG;c.5043+1G>T;c.5095C>T;c.5101C>T;c.5168+2T>C;c.5208dupC;c.5392C>T;c.5464A>C;c.5481-1G>C;c.5573T>C;c.5581dupC;c.5581C>T;c.5617C>T;c.5618G>A;c.5632delC;c.5636+2T>A;c.5648G>A;c.5660C>T;c.5797delA;c.5824G>T;c.5857-2A>G;c.5886_5889delCTTT;c.5899C>T;c.5945-1G>A;c.5945G>A;c.5967C>G;c.5968C>T;c.6025delG;c.6051+1G>A;c.6070C>T;c.6196C>T;c.6211C>T;c.6231dupG;c.6238-2A>C;c.6321G>A;c.6439-2A>G;c.6487G>A;c.6498C>A;c.6557T>C

Mucopolysaccharidosis, type 3B (Sanfilippo B)

Descripción enfermedad:
Mucopolysaccharidosis, type 3B, also known as Sanfilippo syndrome B, is an autosomal recessive lysosomal storage disorder characterized by the accumulation of heparan sulfate. Clinically, patients have progressive neurodegeneration, behavioral problems, mild skeletal changes, and shortened life span. The clinical severity ranges from mild to severe (Chinen et al., 2005).

c.217_221dupGCGCG;c.358G>T;c.383+1G>T;c.384-1G>A;c.419A>G;c.480delT;c.507_516delCGGCCAGGAG;c.503G>A;c.648dupC;c.694C>T;c.700C>T;c.798_805delCAGTTGGG;c.838_841delCTTC;c.867delC;c.889C>T;c.944dupA;c.1006G>T;c.1211G>A;c.1444C>T;c.1447dupT;c.1597C>T;c.1674C>G;c.1693C>T;c.1694G>A;c.1834A>G;c.1876C>T;c.1915G>T;c.1927C>T;c.1944dupG;c.1946G>T;c.1949G>A;c.2021G>A;c.2116C>T

N-acetylglutamate synthase deficiency

Descripción enfermedad:
N-acetylglutamate synthetase deficiency follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the NAGS gene located on chromosomal region 17q21.31. The age of onset is infantile, etc/. This disease is characterized by hyperammonemia, vomiting, hyperactivity or lethargy, diarrhoea, poor feeding, seizures, hypotonia, delayed psychomotor development and respiratory distress. The prevalence is <1:1,000,000.

c.570G>A;c.622C>T;c.916-2A>T;c.971G>A;c.1025delG;c.1289T>C;c.1299G>C;c.1307dupT;c.1323C>G;c.1450T>C

Nijmegen breakage syndrome

Descripción enfermedad:
The Nijmegen breakage syndrome and the phenotypically indistinguishable Berlin breakage syndrome are autosomal recessive chromosomal instability syndromes characterized by microcephaly, growth retardation, immunodeficiency, and predisposition to cancer. Ataxia-telangiectasia variant-1 is the designation applied to the Nijmegen breakage syndrome and AT variant-2 is the designation for the Berlin breakage syndrome, which differ only in complementation studies. Cells from NBS/BBS patients are hypersensitive to ionizing radiation with cytogenetic features indistinguishable from those of ataxia-telangiectasia (AT; 208900), but NBS/BBS patients have a distinct clinical phenotype.The clinical features of LIG4 syndrome (606593), caused by mutation in the LIG4 gene (601837), resemble those of NBS.

c.2235-2A>G;c.2234+2T>G;c.2194C>T;c.2188C>T;c.2185-1G>A;c.2184+1G>A;c.2165G>A;c.2161G>T;c.2140C>T;c.2117C>G;c.2108_2109dupTT;c.2083G>T;c.2071-1G>A;c.2071-1G>C;c.2071-2A>C;c.2070+2T>G;c.2056A>T;c.2049_2050delAAinsT;c.2041C>T;c.2000_2001delCT;c.1986_1999delGGTGATTAAAAACT;c.1974delA;c.1958dupA;c.1903A>T;c.1854_1857delTGAA;c.1848delA;c.1846-1G>A;c.1750G>T;c.1747C>T;c.1723G>T;c.1716dupA;c.1647_1651delAAAAA;c.1648_1651delAAAA;c.1651dupA;c.1640delC;c.1587dupA;c.1553C>G;c.1550dupA;c.1502G>A;c.1483_1484delCCinsA;c.1474C>T;c.1419_1431dupAGAAATGTCTTCA;c.1399G>T;c.1397+1_1397+9delGTCTGTTTTinsACA;c.1397+1delG;c.1397+2T>A;c.1396dupA;c.1255_1258delAATA;c.1171C>T;c.1142delC;c.1125G>A;c.1125-1G>A;c.1125-2A>G;c.1124+2T>G;c.1124+1G>A;c.1124+1G>C;c.1124G>A;c.1089C>A;c.1040C>G;c.1030C>T;c.995-1G>C;c.995-2A>C;c.995-2A>G;c.994+1G>T;c.976C>T;c.935T>A;c.917delC;c.897-2A>T;c.871C>T;c.842dupT;c.842T>G;c.836_839delAGAC;c.817dupA;c.808_809delGT;c.741_742dupGG;c.702+1G>A;c.702+1G>C;c.702+1G>T;c.698_701delAACA;c.697A>T;c.681delT;c.657_661delACAAA;c.591_603delCCCACCTCTTGATinsTTG;c.585-1G>A;c.585-2A>G;c.565C>T;c.531delT;c.481-2A>G;c.481-2A>T;c.445delC;c.383T>G;c.330T>G;c.325G>T;c.320+1G>A;c.317dupT;c.306delT;c.265C>T;c.222T>G;c.212_215delATTC;c.210_211delTA;c.211_212insGA;c.188delT;c.183delT;c.181_182delGA;c.178dupA;c.175C>T;c.163_171+3delACCAACCTGGTA;c.171+1G>A;c.156_157delTT;c.141_142delGT;c.127C>T;c.123delC;c.115delC;c.93_94delTG;c.88_89delAA;c.55_56delTT;c.37+1G>A;c.2T>C

Chronic granulomatous disease due to deficiency of NCF-1

Descripción enfermedad:
Chronic granulomatous disease due to deficiency of NCF-1 is a disorder characterized by the inability of neutrophils and phagocytes to kill microbes that they have ingested. Patients suffer from life-threatening bacterial/fungal infections.

c.75_76delGT;c.125G>A;c.186dupA;c.271C>T;c.333T>A;c.579G>A

Chronic granulomatous disease due to deficiency of NCF-2

Descripción enfermedad:
Chronic granulomatous disease due to deficiency of NCF-2 is a disorder characterized by the inability of neutrophils and phagocytes to kill microbes that they have ingested. Patients suffer from life-threatening bacterial/fungal infections.

c.1171_1175delAAGCT;c.1026+1G>C;c.835_836delAC;c.565C>T;c.482delA;c.399_400dupGA;c.383C>T;c.366+1G>A;c.366+1G>C;c.304C>T;c.298C>T;c.257+1G>A

Charcot-Marie-Tooth disease, type 4D

Descripción enfermedad:
Charcot-Marie-Tooth disease type 4D follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the NDRG1 gene located on chromosomal region 8q24.22. The age of onset is infantile, etc/. This disease is characterized by demyelination and hearing loss.

c.928C>T;c.681dupC;c.538-1G>A;c.442C>T;c.205+1G>A;c.16C>T

Nemaline myopathy type 2, autosomal recessive

Descripción enfermedad:
Nemaline myopathy type 2 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the NEB gene located on chromosomal region 2q23.3. The age of onset is infantile or adult. This disease is characterized by hypotonia, weakness and depressed or absent deep tendon reflexes, with pathologic evidence of nemaline bodies (rods) on muscle biopsy. The prevalence is 1:100,000-9:100,000 and the incidence is 1/50.000 newborn.

c.25509+2T>A;c.25445C>A;c.25441C>T;c.25402+1G>A;c.25288C>T;c.25279G>T;c.25256-1G>T;c.25163-2A>C;c.25162+1G>A;c.25162+1G>C;c.25162+1G>T;c.24871-9_24872delCTGCATCAGGT;c.24840_24841delAG;c.24778-2A>C;c.24770_24771delTT;c.24771delT;c.24744_24745delAA;c.24742G>T;c.24693C>G;c.24685-2A>G;c.24654_24655delAG;c.24632_24633delCT;c.24582_24585dupTATT;c.24559C>T;c.24500_24503dupTGTT;c.24499-1G>A;c.24498+1G>A;c.24482_24488delAAGAAAA;c.24473_24476dupAACA;c.24468_24469delAG;c.24458_24461dupAGAT;c.24444_24447delACCT;c.24414C>A;c.24410T>A;c.24405+1G>A;c.24372_24375delAAGA;c.24372_24375dupAAGA;c.24325G>T;c.24318_24319insAA;c.24314_24317dupTGTT;c.24317T>A;c.24312+2T>C;c.24294_24297dupTCAA;c.24282_24283delAG;c.24219+1G>A;c.24218C>A;c.24156delG;c.24127-1_24134delGGTGTTGTA;c.24129_24133dupGTTGT;c.24127-1G>A;c.24127-1G>C;c.24094C>T;c.23940+1G>A;c.23939C>A;c.23848-1G>C;c.23847+2T>C;c.23556+1G>C;c.23556+1G>T;c.23526_23527delAG;c.23500_23503dupGTTT;c.23483delT;c.23346+2T>A;c.23010+2T>C;c.22905+2T>G;c.22905+1G>A;c.22801-1G>A;c.22746delG;c.22696-1G>C;c.22695+2T>C;c.22594C>T;c.22584+1G>C;c.22378-1G>A;c.22275C>G;c.22243delG;c.22192C>T;c.21841-2A>G;c.21735+1G>A;c.21321C>G;c.21312+1G>A;c.21103delG;c.21093_21094delAG;c.21076C>T;c.20889dupT;c.20858delT;c.20845dupA;c.20788-1G>A;c.20787+2T>C;c.20659C>T;c.20577+2T>C;c.20514C>A;c.20467-1G>T;c.20158-1G>C;c.20157+2T>C;c.14805G>A;c.19836+1G>T;c.19712_19716delCTTATinsGAG;c.19405C>T;c.19207-1G>A;c.19097G>T;c.18891+1G>A;c.18862_18872delGTCCGAAACGC;c.18865C>T;c.18808C>T;c.18676C>T;c.18597delA;c.18471+1G>C;c.18261+1G>T;c.17845-1G>A;c.17557_17558delGA;c.17541dupA;c.17262G>A;c.16620T>A;c.16273C>T;c.12238_12239delAT;c.12018+1G>A;c.11909_11910+4delAAGTAA;c.11910+1G>A;c.11825G>A;c.11806-1G>A;c.11627G>A;c.11602-2A>C;c.11585_11586delATinsC;c.11289+1G>C;c.11181+2T>C;c.11164C>T;c.11076+1G>A;c.10899G>A;c.10872+1G>T;c.10560+1G>A;c.9831+1G>A;c.9724-1G>A;c.9724-2A>G;c.9619-1G>A;c.9619-2A>G;c.9485delT;c.9465delC;c.9459G>A;c.9440G>A;c.9428C>G;c.9414+1G>A;c.9414+1G>T;c.9246G>A;c.9102+1G>A;c.9046C>T;c.8994+2T>C;c.8889+1G>A;c.8887A>T;c.8860delG;c.8392_8395dupTATC;c.8374-1G>A;c.8265+1G>A;c.8031_8041delAAATAAACGAG;c.8038C>T;c.7647C>G;c.7523_7526delTCAA;c.7432-2A>G;c.7266_7268delAGGinsTC;c.7228-1G>A;c.7227+2T>C;c.6937C>T;c.6813_6814delCT;c.6808-2A>T;c.6385C>T;c.6183+2T>A;c.6183+1G>A;c.6105dupT;c.6078delA;c.6076-1G>T;c.6076-2A>C;c.6076-2A>G;c.6075+1G>A;c.5722delA;c.5574C>G;c.5452-2A>G;c.5364G>A;c.5344-1G>A;c.5344-1G>C;c.5031+1G>A;c.4720-2A>G;c.4719+2T>C;c.4506+1G>A;c.4300-2A>C;c.3988-1G>A;c.3987+1_3987+2delGTinsTG;c.3987+1G>A;c.3880-1G>T;c.3880-2A>G;c.3879+1G>A;c.3858C>A;c.3774+2T>C;c.3774+1G>A;c.3567+1G>A;c.3567+1G>C;c.3389_3390delAT;c.3255+1G>A;c.3255+1G>C;c.3255+1G>T;c.3043-1G>A;c.2944-1G>A;c.2943+1G>A;c.2920C>T;c.2784delT;c.2751delT;c.2659G>T;c.2416-1G>C;c.2415+2T>C;c.2415+1G>A;c.2415+1G>T;c.2391_2392delAG;c.2385delA;c.2310+2T>A;c.2212-2A>G;c.2211+1G>A;c.2173G>T;c.1897-1G>A;c.1802_1803delAT;c.1674+2T>C;c.1674+1G>T;c.1623delT;c.1570-2_1574delAGTTAAA;c.1570-2A>G;c.1569+1G>A;c.1471-1G>A;c.1470+1G>A;c.1366-2A>G;c.1365+2T>C;c.1258-2A>G;c.1161C>G;c.1153-2A>G;c.1152+1G>A;c.927+1G>A;c.843T>G;c.823-2A>G;c.613-1G>C;c.613-2A>G;c.507+1G>A;c.412C>T;c.295-1G>T;c.294+2T>C;c.78+1G>A;c.37-1G>A;c.37-1G>C;c.36+1G>T

Dyskeratosis congenita, autosomal recessive type 2

Descripción enfermedad:
Dyskeratosis congenita type 2 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the NHP2 gene located on chromosomal region 5q35.3. The age of onset is variable from infancy to adult. It is a multisystem disorder caused by defective telomere maintenance. Clinical manifestations include mucocutaneous abnormalities, bone marrow failure, and an increased predisposition to cancer, among other variable features.

c.460T>A;c.415T>C;c.289_290delAT

Dyskeratosis congenita, autosomal recessive type 1

Descripción enfermedad:
Dyskeratosis congenita autosomal recessive type 1 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the NOP10 gene located on chromosomal region 15q14. The age of onset is infantile. This disease is characterized by the mucocutaneous triad of abnormal skin pigmentation, nail dystrophy and mucosal leucoplakia. The prevalence is 1:1,000,000.

c.100C>T

Niemann-Pick disease, type C1

Descripción enfermedad:
Niemann-Pick disease type C1 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the NPC1 gene located on chromosomal region 18q11.2. The age of onset varies between the perinatal period and the age of 50 years or more. This disease is characterized by hepatosplenomegaly and progressive neurological involvement. The prevalence is 1/130,000.

c.3754+1G>A;c.3754+1G>C;c.3754+1G>T;c.3742_3745delCTCA;c.3734_3735delCT;c.3666_3672delGATATTC;c.3662delT;c.3639G>C;c.3634G>T;c.3611_3614delTTAC;c.3613dupA;c.3614C>A;c.3614C>G;c.3612_3613delTAinsG;c.3592-1G>C;c.3591+2T>C;c.3591+1G>A;c.3570_3573dupACTT;c.3562delG;c.3557G>A;c.3503G>A;c.3493G>A;c.3467A>G;c.3461T>A;c.3451G>A;c.3425T>C;c.3417_3423delTGGAGTT;c.3325delA;c.3309dupT;c.3259T>C;c.3246-2A>G;c.3234_3237dupATTT;c.3229C>T;c.3182T>C;c.3175C>T;c.3107C>T;c.3104C>T;c.3042-1G>A;c.3042-2delA;c.3019C>G;c.2972_2973delAG;c.2974G>A;c.2974G>C;c.2974G>T;c.2965_2966delAG;c.2932C>T;c.2912-2A>C;c.2907_2908dupTT;c.2893C>T;c.2873G>A;c.2872C>T;c.2861C>T;c.2848G>A;c.2842G>A;c.2830G>A;c.2819C>T;c.2795dupA;c.2775delC;c.2764C>T;c.2761C>T;c.2728G>A;c.2712delG;c.2713C>T;c.2683dupG;c.2670C>G;c.2621A>T;c.2604+1G>A;c.2474A>G;c.2451_2454delGTTT;c.2366G>A;c.2324A>C;c.2302dupG;c.2286_2287delCT;c.2230_2231delGT;c.2213C>A;c.2201G>T;c.2196dupT;c.2177G>C;c.2131-2_2131delAGA;c.2128C>T;c.2072C>T;c.2054T>C;c.2050C>T;c.1990G>A;c.1948-1G>A;c.1948-2A>T;c.1947+5G>C;c.1947+2T>A;c.1947+2T>G;c.1947+1G>A;c.1920delG;c.1819C>T;c.1800delC;c.1761delT;c.1711delT;c.1628delC;c.1628C>T;c.1339C>T;c.1327-1G>A;c.1327-1G>C;c.1301C>T;c.1219C>T;c.1211G>A;c.1210C>T;c.1171G>T;c.1142G>A;c.1070C>T;c.1065delC;c.1042C>T;c.1033_1034delTT;c.1030delT;c.973_974dupGA;c.956-1G>A;c.881+1G>T;c.852delT;c.839delT;c.813_815delCAT;c.721C>T;c.631+2T>C;c.629delC;c.530G>A;c.526delC;c.500C>G;c.451_452delAG;c.433C>T;c.425_428delAAGA;c.423_424dupGA;c.416dupC;c.410C>T;c.397delG;c.395delC;c.352_353delAG;c.337T>C;c.306T>G;c.144_145insT;c.67delC;c.58-2A>T

Niemann-pick disease, type C2

Descripción enfermedad:
Niemann-Pick disease type C2 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the NPC2 gene located on chromosomal region 14q24.3. The age of onset varies between the perinatal period and the age of 50 years or more. This disease is characterized by hepatosplenomegaly and progressive neurological involvement. The prevalence is 1/130,000.

c.436C>T;c.422G>A;c.364-2A>G;c.358C>T;c.352G>T;c.295T>C;c.199T>C;c.190+5G>A;c.141C>A;c.133C>T;c.115G>A;c.82+2T>C;c.58G>T;c.27delG;c.3G>C

Nephrotic syndrome, type 1

Descripción enfermedad:
Nephrotic syndrome type 1 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the NPHS1 gene located on chromosomal region 19q13.12. The age of onset is fetal- infantile. This disease is characterized by fetal proteinuria and nephritic infantile syndrome. The prevalence is 1 in 8 200 births.

c.3613delT;c.3595-2A>G;c.3594+1G>A;c.3478C>T;c.3442C>T;c.3388-1G>A;c.3388-2A>G;c.3356_3357dupGG;c.3325C>T;c.3312-1G>A;c.3287-2A>G;c.3250delG;c.3250dupG;c.3167-1G>A;c.3115dupC;c.3109+1G>A;c.3027C>G;c.3006_3012delTCTACAG;c.2944dupA;c.2928G>T;c.2927+1G>A;c.2905delC;c.2847_2853delTGTGAGT;c.2816-4_2822delATAGGCCGCCC;c.2783C>A;c.2770_2776delAACGCCC;c.2664-4_2670delCTAGGTACACG;c.2663_2663+9delGGTGAGCCCA;c.2663+2T>G;c.2625G>A;c.2618_2620delTCAinsCC;c.2606_2607dupCC;c.2596C>T;c.2549_2558delCTGCAGCTGG;c.2540_2543delCTAA;c.2515delC;c.2500G>T;c.2491C>T;c.2442C>G;c.2417C>A;c.2335-1G>A;c.2227delC;c.2216C>T;c.2206G>A;c.2172_2173delTG;c.2156_2163delTGCACTGC;c.2160dupC;c.2126T>G;c.2120G>A;c.2071+2T>C;c.2043G>T;c.2023_2024delGC;c.1971delC;c.1954C>T;c.1931-1G>A;c.1928T>C;c.1868G>T;c.1829T>A;c.1801G>C;c.1760T>G;c.1757+1G>A;c.1756A>G;c.1745delA;c.1715G>A;c.1707C>G;c.1701C>A;c.1672C>T;c.1583G>T;c.1481delC;c.1394G>A;c.1369delG;c.1337T>A;c.1334G>A;c.1316-2A>G;c.1307_1308dupAC;c.1292dupA;c.1275delC;c.1250G>T;c.1234G>T;c.1138C>T;c.1135_1136delCG;c.1135C>T;c.1134G>A;c.1126C>G;c.1103C>T;c.1102C>T;c.1099C>T;c.1096A>C;c.1040G>A;c.1020delT;c.1019C>A;c.1013-1G>C;c.866G>A;c.851delC;c.808G>T;c.802C>T;c.793T>C;c.736G>T;c.692C>A;c.661_662delAG;c.619delC;c.609-2A>C;c.595delG;c.574C>T;c.565G>T;c.534delG;c.532C>T;c.515_517delCCA;c.516delC;c.512T>A;c.500C>T;c.479G>C;c.468C>G;c.398-1G>A;c.398-2A>G;c.397+2T>C;c.320C>T;c.319G>A;c.313G>A;c.286C>G;c.248dupA;c.191G>C;c.174delT;c.139delG;c.121_122delCT;c.58+1G>A;c.58+1G>T

Nephrotic syndrome, type 2

Descripción enfermedad:
Nephrotic syndrome, type 2 (NPHS2) is an autosomal recessive disorder characterized clinically by childhood onset of proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Kidney biopsies show nonspecific histologic changes such as minimal change, focal segmental glomerulosclerosis (FSGS), and diffuse mesangial proliferation. The disorder is resistant to steroid treatment and progresses to end-stage renal failure in the first or second decades (Fuchshuber et al., 1996). Some patients show later onset of the disorder (Tsukaguchi et al., 2002).

c.964C>T;c.948delT;c.890C>T;c.874-1G>A;c.874-2A>C;c.873+2T>A;c.873+1G>A;c.871C>T;c.868G>A;c.859C>T;c.855_856delAA;c.851C>T;c.812C>T;c.795-1G>A;c.779T>A;c.738+2T>C;c.685C>T;c.643C>T;c.586C>T;c.538G>A;c.535-1G>T;c.503G>A;c.502C>T;c.479A>G;c.452-1G>A;c.451+2T>A;c.412C>T;c.385C>T;c.378+1G>A;c.369delC;c.275-2A>G;c.249delG;c.211C>T;c.156delG;c.138_142dupGGGCT;c.115C>T;c.104dupG

Adrenal hypoplasia, congenital

Descripción enfermedad:
Congenital adrenal hypoplasia follows an X-linked pattern of inheritance and is caused by pathogenic variants in the NR0B1 gene located on chromosomal region Xp21.2. The age of onset is infantile. This disease is characterized by adrenal insufficiency with vomiting, feeding difficulty, dehydration, and shock caused by a salt-wasting episode and hypoglycemia.

c.1364_1365delCA;c.1319A>T;c.1316T>G;c.1301delT;c.1274G>T;c.1231_1234delCTCA;c.1197C>A;c.1183C>T;c.1169-1G>A;c.1146G>T;c.1142T>A;c.1141C>T;c.1138T>G;c.1107G>A;c.1094T>C;c.890T>C;c.873G>C;c.872G>C;c.847C>T;c.844C>T;c.813C>G;c.800G>C;c.788T>A;c.765C>A;c.754delC;c.745_746delAA;c.708G>A;c.704G>A;c.591C>A;c.551_552delAA;c.548delG;c.548dupG;c.543delA;c.516G>A;c.513G>A;c.501delA;c.388_389delTA;c.327C>A;c.315G>A;c.273C>A;c.116G>A;c.109C>T

Enhanced S-cone syndrome (Goldmann-Favre); Retinitis pigmentosa, type 37

Descripción enfermedad:
Enhaced S-Cone Syndrome follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the NR2E3 gene located on chromosomal region 15q23. The age of onset is infantile. This disease is characterized by night blindness, reduced bilateral visual acuity, and typical fundus findings (progressive pigmentary degenerative changes, macular edema, retinoschisis). Mutations in the NR2E3 gene can also cause retinitis pigmentosa 37 (RP37). RP37 is a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision.

c.119-2A>C;c.166G>A;c.226C>T;c.298_299delTG;c.311G>A;c.373C>T;c.724_725delTC;c.926G>T;c.932G>A;c.1034_1038delTGCAG

Insensitivity to pain, congenital, with anhidrosis

Descripción enfermedad:
Insensitivity to pain, congenital, with anhidrosis follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the NTRK1 gene located on chromosomal region 1q23.1. The age of onset is infantile. This disease is characterized by anhidrosis, insensitivity to pain, self-mutilating behavior and episodes of fever.

c.25C>T;c.207_208delTG;c.360-2A>C;c.424G>T;c.526C>T;c.1076A>G;c.1196-1G>A;c.1444A>T;c.1550G>A;c.1660delC;c.1727delT;c.1729G>C;c.1759A>G;c.1860_1861insT;c.1926_1927insT;c.1946G>A;c.2020G>T;c.2046+1G>T;c.2084C>T;c.2281C>T;c.2339G>C

Gyrate atrophy of choroid and retina

Descripción enfermedad:
Gyrate atrophy of choroid and retina follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the OAT gene located on chromosomal region 10q26.13. The age of onset is infantile. This disease is characterized by gyrate atrophy of the choroid and retina that begins during childhood with myopia and night blindness, followed by concentric shrinking of the visual field (tunnel vision) and a peculiar aspect of retinopathy on the funduscopy. Patients can also present with ornithinemia.

c.1307T>A;c.1276C>T;c.1250C>T;c.1205T>C;c.1201G>T;c.1192C>T;c.1186C>T;c.1181G>A;c.1180T>C;c.1124G>C;c.1058G>A;c.1031delA;c.994G>A;c.991C>T;c.955C>T;c.952delG;c.952G>A;c.901-2A>G;c.897C>G;c.824G>A;c.812G>A;c.808G>C;c.800C>T;c.772-1G>A;c.749G>C;c.748C>T;c.734A>G;c.722C>T;c.710G>A;c.698A>G;c.677C>T;c.627T>A;c.596C>A;c.550G>A;c.542C>T;c.539G>C;c.533_537delGGGGT;c.533G>A;c.461G>T;c.425-4_429delATAGGAGTG;c.425G>A;c.425-2A>G;c.381dupT;c.362G>A;c.311A>G;c.278G>T;c.272G>A;c.268C>G;c.267C>A;c.163T>C;c.159delC;c.3G>A

Oculocutaneous albinism type 2

Descripción enfermedad:
Oculocutaneous albinism type 2 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the OCA2 gene located on chromosomal region 15q12-q13. The age of onset is infantile. This disease is characterized by variable hypopigmentation of the skin and hair, numerous characteristic ocular changes and misrouting of the optic nerves at the chiasm. The prevalence is 1/38,000-1/40,000

c.2425T>A;c.2344G>A;c.2339G>A;c.2338+2T>G;c.2228C>T;c.2177_2181delTCCTG;c.2080-1G>A;c.2055delT;c.2037G>C;c.2020C>G;c.1960delG;c.1842+1G>T;c.1503+5G>A;c.1465A>G;c.1427A>G;c.1364+1G>T;c.1327G>A;c.1211C>T;c.1183A>C;c.1182+2T>C;c.1182+1G>A;c.1182G>A;c.1044+1G>T;c.1025A>G;c.867delC;c.819_822delCTGGinsGGTC;c.807+1G>T;c.593C>T;c.440dupT;c.157delA;c.79G>A

Lowe Syndrome; Dent disease type 2

Descripción enfermedad:
Dent disease type 2 and Lowe syndrome follow an X-linked pattern of inheritance and are caused by pathogenic variants in the OCRL gene located on chromosomal region Xq25-q26. Dent disease type 2 is a type of Dent disease in which patients have the manifestations of Dent disease type 1 associated with extra-renal features: hypercalciuria and low-molecular-weight (LMW) proteinuria. In addition, these patients may also have nephrocalcinosis, nephrolithiasis, hematuria, hypophosphatemia and/or renal insufficiency. The features of Lowe syndrome are hydrophthalmia, cataract, mental retardation, vitamin D-resistant rickets, amino aciduria, and reduced ammonia production by the kidney.

c.563+1G>C;c.912_913delAG;c.955C>T;c.1003C>T;c.1098delC;c.1127A>G;c.1439A>G;c.1480C>T;c.1502G>A;c.1573C>T;c.1575C>G;c.1576A>C;c.1579C>T;c.1624C>T;c.1717-1G>A;c.2302C>T;c.2363_2364delTG;c.2406dupA;c.2431C>T;c.2473-2A>G;c.2533C>T;c.2538delA;c.2566delG;c.2585-1G>A;c.2585-1G>T

3-methylglutaconic aciduria, type 3

Descripción enfermedad:
3-methylglutaconic aciduria type 3 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the OPA3 gene located on chromosomal region 19q13.32. The age of onset is infantile. This disease is characterized by the association of optic atrophy and choreoathetosis with 3-methylglutaconic aciduria. The prevalence is 1:10,000-5:10,000.

c.220delG;c.415C>T;c.143-1G>C;c.142+1G>A

Osteopetrosis, autosomal recessive type 5

Descripción enfermedad:
Osteopetrosis, autosomal recessive type 5 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the OSTM1 gene located on chromosomal region 6p21. The age of onset is infantile. This disease is characterized by osteopetrosis, agenesis del cuerpo calloso, atrofia cerebral e hipocampo pequeño.

c.415_416delAG;c.36T>A

Ornithine transcarbamylase deficiency

Descripción enfermedad:
Ornithine transcarbamylase deficiency follows an X-linked pattern of inheritance and is caused by pathogenic variants in the OTC gene located on chromosomal region Xp11.4. The age of onset is infantile. This disease is characterized by severe neonatal hyperammonemic coma that generally proves to be fatal, in males. Females may be also affected by symptoms with various degrees of intensity, ranging from dislike for proteins to chronic vomiting, growth retardation, hypotonia, psychomotor retardation, hyperammonemic coma, or psychiatric disorders. The prevalence is 1:80,000.

c.1A>G;c.1A>T;c.2T>C;c.3G>A;c.29_32delACAA;c.42delT;c.53delA;c.67C>T;c.77G>A;c.77+1G>A;c.77+1G>T;c.78-1G>C;c.94C>T;c.106C>T;c.118C>T;c.119G>A;c.122A>G;c.127C>T;c.131C>T;c.133C>G;c.134T>C;c.140delA;c.140_141insG;c.140A>T;c.143T>C;c.145A>C;c.148G>A;c.148G>T;c.154G>A;c.154G>T;c.155A>G;c.156A>T;c.158T>C;c.158T>G;c.163T>G;c.167T>C;c.170T>A;c.174G>A;c.179C>T;c.188T>C;c.200T>G;c.205C>T;c.216+1delG;c.216+1G>A;c.216+1G>T;c.217-1G>A;c.227T>C;c.231G>T;c.232C>T;c.236G>A;c.238A>G;c.240G>T;c.243_245delCTT;c.245T>G;c.247G>C;c.248G>A;c.254T>C;c.259G>A;c.264A>T;c.268A>G;c.269G>A;c.270T>G;c.271delA;c.274C>G;c.274C>T;c.275G>A;c.275G>C;c.275G>T;c.277A>G;c.281G>C;c.284T>C;c.298+1_298+5delGTAAG;c.298+1G>A;c.298+1G>T;c.298+2T>G;c.299G>A;c.305C>A;c.314G>T;c.316G>A;c.317G>A;c.317G>T;c.330delT;c.332T>C;c.350A>G;c.350A>T;c.359_360delTG;c.364_365insTT;c.365A>G;c.376delG;c.377A>G;c.386G>A;c.386G>C;c.386+1G>A;c.386+1G>T;c.386+2T>C;c.387-2A>C;c.387-2A>G;c.387-2A>T;c.390_392dupATT;c.391_397dupTTGTCTA;c.392T>C;c.394T>C;c.395C>T;c.403delG;c.404C>A;c.407A>T;c.409G>A;c.416T>C;c.418G>C;c.421C>G;c.421C>T;c.422G>A;c.422G>C;c.425T>A;c.430A>T;c.437C>G;c.443T>C;c.443T>G;c.444G>C;c.444G>T;c.451delC;c.452T>G;c.455C>T;c.460G>T;c.463G>C;c.463G>T;c.464C>A;c.476T>C;c.479T>A;c.479T>C;c.479T>G;c.481A>G;c.482A>G;c.484G>A;c.484G>C;c.485G>A;c.490T>C;c.491C>G;c.493G>T;c.501C>A;c.501C>G;c.503A>C;c.503A>G;c.504T>A;c.505C>G;c.506C>T;c.514A>T;c.516C>G;c.517C>G;c.520G>C;c.524A>G;c.524A>T;c.526T>C;c.527A>G;c.532_537delACGCTC;c.533C>T;c.536T>C;c.540+1G>C;c.540+1G>T;c.540+2T>A;c.540+2T>C;c.540+265G>A;c.541-2A>G;c.542A>G;c.562_563delGG;c.562G>C;c.563G>T;c.571C>T;c.576C>G;c.577T>C;c.577T>G;c.578G>A;c.586delG;c.583G>A;c.586G>A;c.586G>T;c.587A>T;c.589G>A;c.589G>T;c.590G>A;c.593A>T;c.594C>A;c.595A>G;c.596A>G;c.602T>C;c.604C>T;c.605A>C;c.608C>G;c.613A>G;c.615G>C;c.617T>G;c.618G>C;c.620G>A;c.621C>A;c.622G>A;c.626C>T;c.628A>C;c.634G>T;c.640C>T;c.643C>T;c.645dupT;c.646C>G;c.650C>A;c.658C>G;c.659C>T;c.663G>C;c.663+1G>A;c.663+1G>T;c.663+2T>C;c.665delG;c.664-1G>A;c.673C>A;c.674C>G;c.674C>T;c.698C>T;c.700G>T;c.716A>G;c.716A>T;c.717G>C;c.717+1G>A;c.717+1G>T;c.717+2T>C;c.718-2A>G;c.725C>T;c.731T>A;c.740C>A;c.757G>A;c.757G>C;c.759delA;c.779T>C;c.785C>A;c.785C>T;c.787G>A;c.788A>G;c.790A>G;c.791C>A;c.791C>T;c.793T>C;c.794G>T;c.795G>A;c.799A>C;c.803T>C;c.806G>A;c.808C>T;c.809A>C;c.818delA;c.829C>T;c.830G>A;c.830G>T;c.835C>T;c.867G>T;c.867+1G>A;c.867+1G>T;c.868-2A>T;c.876delA;c.882delT;c.890_893delACTG;c.892_893delTG;c.893G>C;c.903A>T;c.904C>T;c.905A>G;c.905A>T;c.906delC;c.906C>G;c.907T>C;c.907T>G;c.908G>A;c.912G>T;c.914C>A;c.914C>G;c.919A>G;c.928G>T;c.929A>G;c.931G>A;c.941_943delAAG;c.943G>T;c.944T>A;c.944T>G;c.947T>C;c.953C>T;c.958C>T;c.959G>T;c.962C>A;c.976G>A;c.982G>T;c.991A>T;c.994T>A;c.995G>A;c.996G>A;c.1005G>A;c.1005+1G>T;c.1005+2T>C;c.1006-1G>A;c.1006G>T;c.1009G>C;c.1015G>C;c.1018T>C;c.1022T>C;c.1028C>A;c.1033T>C;c.1033T>G;c.1034A>G;c.1042C>T

Osteogenesis imperfecta, type 8

Descripción enfermedad:
Osteogenesis imperfecta type 8 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the P3H1 gene located on chromosomal region 1p34.2. The age of onset is infantile. This disease is characterized by bone fragility, low bone mass and susceptibility to bone fractures. The prevalence is 6:100,000-7:100,000.

c.1656C>A;c.1569+1G>A;c.1473+1G>T;c.1365_1366delAGinsC;c.1346-1G>C;c.1222A>T;c.1171-2A>T;c.1120G>T;c.1102C>T;c.1080+1G>T;c.940+1G>T;c.747delC;c.570_571delTG;c.392C>A

Phenylketonuria

Descripción enfermedad:
Phenylketonuria follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the PAH gene located on chromosomal region 12q23.2. The age of onset is neonatal. This disease is characterized by gradual developmental delay, stunted growth, microcephaly, seizures, tremors, eczema, vomiting, and musty odor. Untreated patients subsequently develop intellectual disability, behavioral disorders (hyperactivity) and motor disorders. The prevalence is 1:2,600-1:200,000.

c.1355dupA;c.1340C>A;c.1314_1315+4delCAGTAA;c.1315+2T>C;c.1315+1G>A;c.1315+1G>T;c.1301C>A;c.1298dupT;c.1293_1294delGA;c.1282C>T;c.1256A>G;c.1252A>C;c.1249T>C;c.1243G>A;c.1241A>G;c.1240T>C;c.1238G>C;c.1223G>A;c.1222C>T;c.1220C>T;c.1219C>T;c.1217T>C;c.1209delT;c.1208C>T;c.1200-1G>A;c.1200-8G>A;c.1199+17G>A;c.1199+2T>G;c.1199+1G>A;c.1199+1G>C;c.1198delA;c.1197A>T;c.1196T>C;c.1184C>A;c.1184C>G;c.1180G>C;c.1180G>T;c.1171_1172delAG;c.1172G>C;c.1171A>G;c.1169A>G;c.1166delC;c.1163T>C;c.1162G>A;c.1162G>C;c.1157A>G;c.1147C>T;c.1139C>T;c.1129delT;c.1114A>T;c.1089delG;c.1076C>G;c.1068C>A;c.1068C>G;c.1066-2A>T;c.1066-3C>T;c.1066-11G>A;c.1065+1G>A;c.1055delG;c.1049C>A;c.1045T>C;c.1042C>G;c.1033G>A;c.1033G>T;c.1030G>A;c.1028A>G;c.1024delG;c.1025C>A;c.1004A>C;c.997C>T;c.992T>C;c.978G>A;c.977G>A;c.975C>G;c.974A>G;c.970-1G>A;c.970-1G>C;c.967_969delACA;c.960G>C;c.955G>T;c.941C>A;c.940C>A;c.934G>T;c.931_932delCT;c.932T>C;c.929C>T;c.926C>A;c.926C>T;c.916delA;c.916A>G;c.913-2A>C;c.913-7A>G;c.912+2T>C;c.912+1G>A;c.910C>T;c.901C>A;c.898G>T;c.896T>G;c.895T>C;c.890G>A;c.887A>G;c.869A>T;c.847A>T;c.844G>A;c.842+5G>A;c.842+4A>G;c.842+3G>C;c.842+2T>A;c.842+1G>A;c.842C>T;c.841C>G;c.841C>T;c.839A>G;c.837delC;c.838G>A;c.836C>T;c.833C>A;c.833C>T;c.830A>G;c.829T>G;c.826A>G;c.824C>G;c.824C>T;c.823C>T;c.818C>T;c.814G>T;c.809G>A;c.806delT;c.806T>A;c.796A>C;c.790delC;c.785T>G;c.782G>A;c.782G>C;c.781C>G;c.781C>T;c.776C>T;c.775G>A;c.770G>T;c.764T>C;c.757G>A;c.755G>A;c.754C>G;c.754C>T;c.745delC;c.745C>T;c.740G>T;c.739G>C;c.737delC;c.737C>A;c.734_735delTGinsCA;c.734T>A;c.734T>C;c.733G>C;c.731C>T;c.728G>A;c.727C>T;c.724C>T;c.722delG;c.722G>A;c.722G>T;c.721C>T;c.694C>T;c.691T>C;c.689T>C;c.688G>A;c.686dupA;c.682G>A;c.673C>A;c.673C>G;c.664_665delGA;c.665A>G;c.662A>G;c.648C>G;c.638T>C;c.635T>C;c.632delC;c.632C>T;c.631C>A;c.618C>A;c.618C>G;c.612T>G;c.611A>G;c.591G>C;c.580_581delCT;c.581T>C;c.569T>C;c.563G>A;c.561G>A;c.558_559delAT;c.556delA;c.547_548delGAinsTT;c.535T>A;c.533A>G;c.529G>A;c.529G>C;c.527G>T;c.526C>T;c.520A>G;c.511G>A;c.510-2A>G;c.509+1G>A;c.508C>G;c.506G>A;c.505C>T;c.503delA;c.504C>A;c.500A>T;c.498C>G;c.490A>G;c.482T>C;c.473G>A;c.472C>T;c.470_471delGAinsAC;c.464G>A;c.464G>C;c.450dupA;c.442-1G>A;c.442-2A>C;c.442-5C>G;c.441+5G>T;c.441+4A>G;c.441+1G>A;c.441+1G>C;c.440C>T;c.434A>T;c.398_401delATCA;c.400C>T;c.385G>T;c.357delC;c.355C>T;c.350delC;c.331C>T;c.329delC;c.320A>G;c.311C>A;c.284_286delTCA;c.283A>T;c.266dupC;c.261C>A;c.250G>T;c.242C>A;c.227A>G;c.226G>T;c.212G>A;c.208_210delTCT;c.204A>T;c.196G>T;c.194T>C;c.169G>A;c.169G>T;c.169-2A>G;c.168+5G>C;c.168_168+1delGGinsAA;c.168+1G>A;c.165delT;c.165T>G;c.164T>C;c.143T>C;c.140C>T;c.136G>A;c.127G>T;c.121C>T;c.116_118delTCT;c.117C>G;c.110T>C;c.60+5G>T;c.60+1G>C;c.58C>T;c.47_48delCT;c.3G>A;c.3G>C;c.1A>G

Pyruvate carboxylase deficiency

Descripción enfermedad:
Pyruvate carboxylase deficiency follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the PC gene located on chromosomal region 11q13.2. The age of onset is infantile. This disease is characterized by metabolic acidosis, failure to thrive, developmental delay, and recurrent seizures. The prevalence is 1:250,000.

c.3409_3410delCT;c.2493_2494delGT;c.2229G>T;c.2114C>A;c.1892G>A;c.1828G>A;c.1748G>T;c.1705A>G;c.1368+1G>A;c.1357C>T;c.1351C>T;c.1043delA;c.1022+1G>A;c.633+2T>C;c.434T>C;c.184C>T;c.52C>T

Propionic acidemia

Descripción enfermedad:
Propionic acidemia follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the PCCA gene located on chromosomal region 13q32.3. The age of onset is infantile. This disease is characterized by life threatening episodes of metabolic decompensation, neurological dysfunction and may be complicated by cardiomyopathy. The prevalence is 1:100,000.

c.69_78delGCAGCTGATG;c.105+1G>A;c.134_135delTA;c.183delA;c.183+2T>C;c.184-1G>A;c.229C>T;c.231+1G>C;c.232-1G>A;c.261dupT;c.284A>G;c.412G>A;c.425G>A;c.431G>T;c.440delC;c.467T>A;c.491T>C;c.548T>G;c.600+1G>A;c.600+1G>T;c.722delG;c.775_779delCTAAT;c.843delT;c.862A>G;c.862A>T;c.863G>A;c.878A>G;c.893A>G;c.915-1G>C;c.937C>T;c.1023dupT;c.1118T>A;c.1190_1193delAATG;c.1226_1227delTT;c.1284+1G>A;c.1426C>T;c.1540+1G>C;c.1540+2T>A;c.1598_1601delTTGT;c.1685C>G;c.1747-1G>C;c.1788G>A;c.1846-1G>A;c.1855C>T;c.1891G>C;c.1899+4_1899+7delAGTA;c.2002G>A;c.2040+1G>T;c.2041-2A>G;c.2056G>T;c.2103delT;c.2118+1G>A

Propionic acidemia

Descripción enfermedad:
Propionic acidemia follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the PCCB gene located on chromosomal region 3q22.3. The age of onset is infantile. This disease is characterized by life threatening episodes of metabolic decompensation, neurological dysfunction and may be complicated by cardiomyopathy. The prevalence is 1:100,000.

c.183+1G>A;c.184-2A>G;c.184-1G>A;c.280G>T;c.331C>T;c.335G>A;c.337C>T;c.372+2T>C;c.446_447delTTinsAAC;c.478_489dupAAGATCTGCAAA;c.489+1G>A;c.517G>C;c.547_548dupGG;c.553C>T;c.554G>A;c.562G>A;c.577_578delTT;c.604-2A>G;c.613dupA;c.622G>A;c.709dupG;c.714+1G>C;c.743C>T;c.823+1G>A;c.823+2T>A;c.824-2delA;c.898dupC;c.944+1G>C;c.945-2A>G;c.1002C>A;c.1026+1G>T;c.1027-2A>C;c.1050dupT;c.1150+2T>C;c.1233dupT;c.1270G>A;c.1278_1291delGGGCATCATCCGGCinsTAGAGCACAGGA;c.1279_1284delGGCATCinsAA;c.1283_1286delTCAT;c.1288C>T;c.1289_1290insT;c.1320dupT;c.1343C>T;c.1360-2A>C;c.1364A>G;c.1376A>G;c.1439_1445delTTGCAGT;c.1458+1G>T;c.1555C>T;c.1558+2T>C;c.1594C>T;c.1598_1600dupCCC;c.1600C>T;c.1616T>C;c.1666A>G

Deafness, autosomal recessive type 23; Usher syndrome, type 1D/F digenic

Descripción enfermedad:
Deafness, autosomal recessive 23 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the PCDH15 gene located on chromosomal region 10q21.1. This is a form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. Usher syndrome type 1 is an autosomal recessive condition characterized by profound congenital hearing impairment with unintelligible speech, early retinitis pigmentosa (usually evident within the first decade), and constant vestibular dysfunction.

c.5680A>T;c.4982_4983insTGAT;c.4958_4961dupTGAT;c.4885delA;c.4569_4572dupATCT;c.4483_4490dupAATACTAT;c.4389-2A>T;c.4384T>C;c.4358+1G>A;c.4328delC;c.4252_4253delGC;c.4242T>A;c.4226+2T>G;c.4226+1G>A;c.4212_4213insGTAG;c.4050T>A;c.3999-1G>C;c.3999-2A>G;c.3998+1G>T;c.3900_3904dupAGATG;c.3822-2A>G;c.3821+2T>C;c.3821+1G>C;c.3807_3813dupAGAAGAT;c.3806_3809delTAGA;c.3746_3749delATCA;c.3733-2A>G;c.3732+1G>A;c.3668delT;c.3517-2A>G;c.3516+1G>T;c.3456dupA;c.3389-1G>T;c.3373C>T;c.3356delT;c.3331C>T;c.3248-2A>G;c.3226delA;c.3138-1G>A;c.3137+2T>A;c.3097delC;c.3038delC;c.2986C>T;c.2884-1G>T;c.2840delG;c.2800C>T;c.2766+2T>C;c.2660_2661delAT;c.2639C>A;c.2502dupA;c.2434dupA;c.2106+2T>C;c.2067C>A;c.2013-2A>G;c.2012+1G>A;c.2012+1G>T;c.1955C>G;c.1942C>T;c.1932+2T>C;c.1930C>T;c.1845_1848delTCAA;c.1821T>G;c.1800-2A>C;c.1785_1786delTC;c.1752C>G;c.1652_1653delAT;c.1642delG;c.1598T>A;c.1320+1G>A;c.1320+1G>C;c.1103delT;c.1021C>T;c.916dupA;c.800G>A;c.748C>T;c.720+1G>A;c.662T>G;c.609+1G>T;c.415C>G;c.415C>T;c.409dupG;c.373_374delTG;c.348dupA;c.289C>T;c.173-1G>A;c.173-2A>T;c.172+1G>C;c.160G>T;c.16delT;c.7C>T

Pyruvate dehydrogenase E1-alpha deficiency

Descripción enfermedad:
Pyruvate dehydrogenase E1-alpha deficiency follows an X-linked pattern of inheritance and is caused by pathogenic variants in the PDHA1 gene located on chromosomal region Xp22.12. The age of onset is variable. This disease is characterized by primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis.The prevalence is >1:40,000 newborn.

c.172-1G>A;c.328C>T;c.536G>A;c.597C>T;c.620C>T;c.754T>C;c.764C>T;c.841T>A;c.874-1G>T;c.887A>C;c.901C>G;c.946-1G>A;c.946G>A;c.972_975dupTTAC;c.975_976insT;c.977G>A;c.1014-2A>G;c.1018C>T;c.1019G>A;c.1024C>T;c.1048_1054delAGTAAGA;c.1050_1053delTAAG;c.1051_1054dupAAGA;c.1057G>A;c.1068dupG;c.1099_1112dupCTTGCCAGTGTGGA;c.1214A>C;c.1246C>T;c.1247G>A;c.1256_1259dupATCA;c.1273_1276dupAAGT;c.1273_1274delAA

Heimler syndrome type 1

Descripción enfermedad:
Heimler syndrome 1 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the PEX1 gene located on chromosomal region 7q21.2. This disease is characterized by sensorineural hearing loss, enamel hyoplasia of the secondary dentition, and nail abnormalities.

c.3750G>A;c.3693_3696delGTCA;c.3580_3581delGA;c.3574C>T;c.3547G>T;c.3505_3517delCAGTTGTTTTCAC;c.3517C>T;c.3455_3456delCT;c.3455_3456dupCT;c.3438+1G>T;c.3379dupC;c.3303_3304dupAT;c.3237_3238delAA;c.3208-1G>A;c.3205C>T;c.2992C>T;c.2927-2A>G;c.2926+2T>C;c.2926+1G>A;c.2922delA;c.2916delA;c.2894T>C;c.2875C>T;c.2859dupT;c.2798dupA;c.2760delA;c.2730delA;c.2723delC;c.2719-2A>G;c.2686C>T;c.2617C>T;c.2614C>T;c.2528G>A;c.2488_2489dupAA;c.2489dupA;c.2391_2392delTC;c.2383C>T;c.2230C>T;c.2176C>T;c.2162_2166delTACTT;c.2137C>T;c.2097dupT;c.2071+2T>C;c.2034_2035delCA;c.1991T>C;c.1964_1970dupAGCCATC;c.1952_1960dupCAGTGTGGA;c.1927dupA;c.1926_1927delAAinsC;c.1921C>T;c.1908delG;c.1897C>T;c.1886_1887delGT;c.1842delA;c.1803+1G>T;c.1792delA;c.1765G>T;c.1716_1717delCA;c.1670+1G>A;c.1670+1G>T;c.1587+2T>C;c.1587+1G>A;c.1527delA;c.1528G>T;c.1522dupG;c.1501_1502delCT;c.1439delT;c.1414C>T;c.1239+1G>A;c.1239+1G>T;c.1155delA;c.1131delA;c.1108delA;c.1076delA;c.1074_1075delGA;c.911_912delCT;c.892_895dupTATA;c.877C>T;c.782_783delAA;c.760dupT;c.734delT;c.657_660delGTCA;c.643_647delACCAA;c.569C>A;c.547C>T;c.473-1G>A;c.473-1G>C;c.472+1G>A;c.431dupC;c.358-1G>T;c.358-2A>C;c.358-2A>G;c.357+1G>A;c.348G>A;c.273+1G>A;c.130-1G>C;c.5G>A;c.3G>A;c.2T>C;c.1A>T

Peroxisome biogenesis disorder type 5A (Zellweger)

Descripción enfermedad:
Peroxisome biogenesis disorder 5A (Zellweger) follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the PEX2 gene located on chromosomal region 8q21.13. The peroxisomal biogenesis disorder (PBD) Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life 

c.865dupA;c.834_838delTACTT;c.789_790delCT;c.739T>C;c.669G>A;c.373C>T;c.355C>T;c.339_345delCAGGTGG;c.279_283delGAGAT;c.163G>A

Peroxisome biogenesis disorder type 2A (Zellweger)

Descripción enfermedad:
Peroxisome biogenesis disorder 2A (Zellweger) follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the PEX5 gene located on chromosomal region 12p13.31. The peroxisomal biogenesis disorder (PBD) Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life 

c.512-2A>G;c.615-1G>A;c.740dupA;c.1342C>T;c.1641T>G;c.1862C>T

Peroxisome biogenesis disorder, type 4A (Zellweger syndrome); Peroxisome biogenesis disorder, type 4B; Heimler syndrome 2

Descripción enfermedad:
Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (Steinberg et al., 2006), Mutations in the PEX6 gene also cause the milder phenotypes peroxisome biogenesis disorder, type 4B (PBD4B) and Heimler syndrome, type 2 (HMLR2). PBD4B includes the overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), which represent milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders (PBDs). The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy, and visual impairment. Children with the NALD presentation may reach their teens, and those with the IRD presentation may reach adulthood (Waterham and Ebberink, 2012). Heimler syndrome, which represents the mildest end of the peroxisomal biogenesis disorder spectrum (PBD1A, 214100), is a rare autosomal recessive disorder characterized by sensorineural hearing loss, enamel hypoplasia of the secondary dentition, and nail abnormalities (Ratbi et al., 2015).

c.2806+1G>A;c.2714G>T;c.2667-2A>C;c.2578C>T;c.2472-2A>G;c.2439dupG;c.2440C>T;c.2362+1G>A;c.2082delT;c.1962-1G>A;c.1947delG;c.1941C>A;c.1930C>T;c.1841delT;c.1715C>T;c.1601T>C;c.1360C>T;c.1338_1339delTG;c.1314_1321delGGAGGCCT;c.1287delC;c.1234-1G>T;c.1233+1G>A;c.1202T>A;c.1130+2T>C;c.1046+1G>A;c.821C>T;c.802_815delGACGGACTGGCGCT;c.689_690dupAG;c.684dupC;c.661G>T;c.654C>G;c.517delA;c.510dupT;c.311delG;c.273G>A

Rhizomelic chondrodysplasia punctata, type 1

Descripción enfermedad:
Rhizomelic chondrodysplasia punctata type 1 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the PEX7 gene located on chromosomal region 6q23.3. The age of onset is early. This disease is characterized by proximal shortening of the humerus and to a lesser degree the femur (rhizomelia), punctate calcifications in cartilage with epiphyseal and metaphyseal abnormalities (chondrodysplasia punctata), coronal clefts of the vertebral bodies, cataracts, postnatal growth deficiency is profound, intellectual disability is severe, seizures. The prevalence is <1:100,000.

c.13_19dupTGCGGTG;c.45_52dupGGGACGCC;c.120C>G;c.130+1G>C;c.131-2A>G;c.183delT;c.188+1G>C;c.189-2A>G;c.277C>T;c.334C>T;c.339+2T>C;c.340-10A>G;c.345T>G;c.357G>A;c.373G>T;c.400G>A;c.429delT;c.508delT;c.527-2A>G;c.532C>T;c.545dupT;c.618G>A;c.633+1G>A;c.649G>A;c.653C>T;c.694C>T;c.748-2A>G;c.774_784delGGCCTCTTGCT;c.854A>G;c.871_874delGGTT;c.875T>A;c.903+1G>C

Neu-Laxova syndrome, type 1; Phosphoglycerate dehydrogenase deficiency

Descripción enfermedad:
Neu-Laxova syndrome is an autosomal recessive lethal multiple malformation syndrome characterized by ichthyosis, marked intrauterine growth restriction, microcephaly, short neck, central nervous system anomalies (lissencephaly, cerebellar hypoplasia and/or abnormal/agenesis of the corpus callosum), limb deformities, hypoplastic lungs, edema, and abnormal facial features including severe proptosis with ectropion, hypertelorism, micrognathia, flattened nose, and malformed ears (Manning et al., 2004). Neu-Laxova syndrome, type 1 (NLS1) is caused by homozygous mutation in the PHGDH gene on chromosome 1p12. Mutation in PHGDH also causes phosphoglycerate dehydrogenase deficiency (PHGDH) deficiency, an allelic disorder with a less severe phenotype. PHGDH is an autosomal recessive inborn error of L-serine biosynthesis that is characterized by congenital microcephaly, psychomotor retardation, and seizures (Jaeken et al., 1996).

c.290+2T>C;c.374C>T;c.403C>T;c.418G>A;c.714delG;c.781G>A;c.793G>A;c.856G>C;c.1030C>T;c.1129G>A;c.1273G>A;c.1468G>A;c.1567C>T

Polycystic kidney disease type 4

Descripción enfermedad:
Polycystic kidney disease type 4 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the PKHD1 gene located on chromosomal region 6p12.3-p12.2. The age of onset is early. This disease is a severe form of polycystic kidney disease affecting the kidneys and, in some cases, the hepatic biliary tract. Up to 50% of the affected neonates die shortly after birth, as a result of severe pulmonary hypoplasia and secondary respiratory insufficiency. In the subset that survives the perinatal period, morbidity and mortality are mainly related to severe systemic hypertension, renal insufficiency, and portal hypertension due to portal-tract fibrosis.

c.12027C>G;c.11785+1G>T;c.11776delG;c.11747C>G;c.11665+1G>A;c.11612G>A;c.11524C>T;c.11363_11372delCTTCCCTGGA;c.11314C>T;c.11311-2A>G;c.11212_11213delAT;c.11147_11150delCTCA;c.11074C>T;c.10972_10973delAT;c.10893_10894delTA;c.10856delA;c.10826delA;c.10735delG;c.10709C>G;c.10637delT;c.10561_10562delCA;c.10461dupG;c.10452dupT;c.10444C>T;c.10418delT;c.10411delG;c.10412T>G;c.10219C>T;c.10199dupT;c.10194delT;c.10186_10190delTACCA;c.10174C>T;c.10136delC;c.10109dupT;c.10036_10045delTGTGCAAGTC;c.10031T>G;c.9998+1G>T;c.9901G>T;c.9856_9859dupAGTT;c.9743delT;c.9719G>A;c.9719G>T;c.9718C>T;c.9689delA;c.9683C>A;c.9646C>T;c.9559delT;c.9530T>C;c.9470_9473dupCCAT;c.9370C>T;c.9319C>T;c.9296C>A;c.9053C>T;c.8958delT;c.8950+1G>T;c.8870T>C;c.8832delT;c.8824C>T;c.8764_8765delAG;c.8677dupC;c.8555-2A>C;c.8555-2A>G;c.8411T>A;c.8408G>A;c.8407T>C;c.8317G>T;c.8303-1G>A;c.8303-2A>G;c.8190delT;c.8162delC;c.8107+1G>C;c.8068T>C;c.8050C>T;c.8011C>T;c.7967_7968delCA;c.7916C>A;c.7912-1G>A;c.7912-2A>G;c.7893delG;c.7866delC;c.7719dupT;c.7713delT;c.7696G>T;c.7560dupT;c.7486+1G>T;c.7351-1G>C;c.7350+1G>T;c.7270delG;c.7194G>A;c.7122delT;c.7084C>T;c.6992T>A;c.6910C>T;c.6907A>T;c.6861delA;c.6809-2A>G;c.6526A>T;c.6499C>T;c.6491-1G>A;c.6490+1G>A;c.6383delT;c.6296_6297delTG;c.6091delG;c.6029delA;c.5912G>A;c.5909-2delA;c.5895dupA;c.5879_5880delCA;c.5825A>G;c.5752-2A>G;c.5751+1G>A;c.5513A>G;c.5485C>T;c.5457_5458delTG;c.5452C>T;c.5448T>A;c.5411delG;c.5372C>T;c.5325_5326delAG;c.5323C>T;c.5237-2A>C;c.5236+1G>A;c.5134G>A;c.5081dupG;c.5060T>C;c.5023delG;c.4890delG;c.4882C>G;c.4870C>T;c.4822_4823delAT;c.4733delA;c.4593dupT;c.4574delC;c.4557delT;c.4417C>T;c.4415delGinsTATTCCCC;c.4292G>A;c.4141delG;c.4121delG;c.3943delC;c.3940delA;c.3766delC;c.3761_3762delCCinsG;c.3561-2A>G;c.3528dupC;c.3463_3464dupCA;c.3463C>T;c.3367G>A;c.3313delT;c.3302delC;c.3229-2A>C;c.3228+1G>C;c.3228+1G>T;c.3097+2T>C;c.2854G>A;c.2827_2828delGA;c.2822-1G>C;c.2813delA;c.2811G>A;c.2810G>A;c.2725C>T;c.2715+1G>C;c.2590delA;c.2452C>T;c.2414C>T;c.2408-2A>G;c.2407+1G>A;c.2346_2352delGCGGACA;c.2341C>T;c.2299_2306delACAGAAGAinsTCTG;c.2279G>A;c.2264C>T;c.2192C>A;c.2180dupA;c.2141-2A>C;c.2140+1G>C;c.2140+1G>T;c.1830T>A;c.1694-1G>A;c.1623_1626dupGTTA;c.1602+1G>A;c.1486C>T;c.1480C>T;c.1458C>A;c.1409delG;c.1205delT;c.1095G>A;c.1068dupT;c.982C>T;c.930delC;c.881-1G>A;c.765C>G;c.748C>T;c.711_714delAATG;c.708-1G>A;c.708-2A>C;c.707+2T>C;c.707+1G>A;c.682A>G;c.664A>G;c.603-1G>A;c.603-2A>G;c.602+1G>A;c.468delT;c.448+2T>C;c.391-1G>C;c.390+1delG;c.383delC;c.370C>T;c.353delG;c.340C>T;c.282-2A>T;c.156dupC;c.107C>T;c.85G>T;c.53-1G>A;c.53-2A>G;c.11G>A;c.4_7delACTG

Infantile neuroaxonal dystrophy type 1

Descripción enfermedad:
Infantile neuroaxonal dystrophy follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the PLA2G6 gene located on chromosomal region 22q13.1. The age of onset is infantile. This disease is a type of neurodegeneration with brain iron accumulation characterized by psychomotor delay and regression, increasing neurological involvement with symmetrical pyramidal tract signs and spastic tetraplegia. INAD may be classic or atypical and patients present with symptoms anywhere along a continuum between the two.

c.2370_2371delTG;c.2370T>G;c.2277-2A>C;c.2246G>C;c.2239C>T;c.2233C>T;c.2222G>A;c.2221C>T;c.2215G>C;c.2129G>A;c.2098C>T;c.2070_2072delTGT;c.1979C>G;c.1978C>T;c.1911delC;c.1904G>A;c.1903C>T;c.1894C>T;c.1799G>A;c.1754C>T;c.1743-1G>C;c.1674delG;c.1634A>C;c.1634A>G;c.1613G>A;c.1612C>T;c.1592-2A>C;c.1547_1548dupCG;c.1509delC;c.1442T>A;c.1427+1G>A;c.1354C>T;c.1351delC;c.1349-2A>G;c.1117G>A;c.1019_1025delGGGCCAA;c.991G>T;c.945_947dupCGC;c.929T>A;c.755delA;c.673C>T;c.517C>T;c.386T>C;c.298C>T;c.217C>T;c.208C>T;c.109C>T;c.3G>T

Ehlers-Danlos syndrome, kyphoscoliotic type, 1

Descripción enfermedad:
Ehlers-Danlos syndrome kyphoscoliotic type, 1 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the PLOD1 gene located on chromosomal region 1p36. The age of onset is early. This disease is characterized by progressive scoliosis from birth, severe muscle hypotonia, hyperextensible joints and fragile eyeballs. The weakness can lead to ocular retinal hemorrhage, glaucoma, coloring of the sclera or even to rupture of the globe. The prevalence is <1:5,000.

c.307C>T;c.468delG;c.543delA;c.607+1G>A;c.720+1G>A;c.1096C>T;c.1120C>T;c.1238+1G>A;c.1611+2T>C;c.1612-2A>G;c.1674C>G;c.1703G>A;c.1792-2delA;c.1792-2A>C;c.1792-2A>G;c.1977G>C;c.2044-2A>G;c.2149C>T;c.2173G>A

Congenital disorder of glycosylation, type 1A

Descripción enfermedad:
Congenital disorder of glycosylation type 1a follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the PMM2 gene located on chromosomal region 16p13.2. The age of onset is infantile. This disease is characterized by highly variable clinical manifestations that may include feeding problems, vomiting, and diarrhea with failure to thrive in infants, and severe encephalopathy with axial hypotonia, abnormal eye movement, marked psychomotor retardation, peripheral neuropathy, cerebellar hypoplasia, stroke-like episodes, and retinitis pigmentosa in late infancy, childhood or adulthood.

c.1A>G;c.24delC;c.26G>A;c.53C>G;c.67-2A>T;c.95_96delTAinsGC;c.95T>G;c.97C>T;c.104T>A;c.109C>T;c.131T>C;c.157C>T;c.178+2T>G;c.179-1G>T;c.189delA;c.190delT;c.193G>T;c.205C>T;c.255+1G>A;c.255+2T>C;c.256-2A>G;c.256-1G>C;c.310C>G;c.323C>T;c.324delG;c.338C>T;c.345dupG;c.347+1G>A;c.348-2A>C;c.348-1G>C;c.349G>C;c.357C>A;c.359T>C;c.367C>T;c.368G>A;c.385G>A;c.392delC;c.395T>C;c.414delA;c.415G>A;c.422G>A;c.430T>C;c.442G>A;c.451_454delGAAA;c.454_455delAA;c.458T>C;c.470T>C;c.484C>T;c.511dupA;c.524-2A>G;c.560G>A;c.563A>G;c.580C>T;c.620T>C;c.623G>C;c.639+1G>A;c.647A>T;c.652C>G;c.653A>T;c.669C>G;c.677C>G;c.691G>A;c.710C>G;c.710C>T;c.722G>C

Pyridoxamine 5'-phosphate oxidase deficiency

Descripción enfermedad:
Pyridoxamine 5'-phosphate oxidase (PNPO) deficiency follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the PNPO gene located on chromosomal region 17q21.32. The age of onset is early. This disease is characterized by onset of severe seizures within hours of birth that are not responsive to anticonvulsants.

c.98A>T;c.264-2A>G;c.364-1G>A;c.399G>A;c.448_451delCCTG;c.471C>A;c.481C>T;c.520C>T;c.673C>T;c.674G>A;c.674G>T;c.685C>T;c.784T>C

POLG-related disorders

Descripción enfermedad:
POLG-related disorders follow an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the POLG gene located on chromosomal region 15q26.1. POLG-related disorders have overlapping signs and symptoms affecting mucle-, nerve-, and brain-related functions. Mitochondrial DNA depletion syndrome 4A, Alpers type (203700) is characterized by the clinical triad of psychomotor regression, seizures, and liver disease, and its prevalence is 1:1,600 newborn. Mitochondrial DNA depletion syndrome-4B (613662) is an autosomal recessive progressive multisystem disorder clinically characterized by chronic gastrointestinal dysmotility and pseudoobstruction, cachexia, progressive external ophthalmoplegia (PEO), axonal sensory ataxic neuropathy, and muscle weakness Another condition caused by mutations in the POLG gene is ataxia neuropathy spectrum (607459), that is characterized by problems with coordination and balance (ataxia) and disturbances in nerve function (neuropathy). The conditions previously named mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO) are now included in the ataxia neuropathy spectrum.

c.3644-1G>A;c.3643+2T>C;c.3630dupC;c.3609_3612dupAACT;c.3527C>A;c.3523C>T;c.3488T>G;c.3483-2A>G;c.3470A>G;c.3409dupG;c.3406G>A;c.3286C>T;c.3240_3242dupCCG;c.3218C>T;c.3151G>C;c.3139C>T;c.3104+2T>A;c.3057G>A;c.2982-1G>C;c.2897T>G;c.2890C>T;c.2870C>T;c.2869G>C;c.2869G>T;c.2864A>G;c.2800_2801delAA;c.2794C>T;c.2740A>C;c.2617G>T;c.2605C>T;c.2591A>G;c.2584G>A;c.2558G>A;c.2557C>T;c.2554C>T;c.2542G>A;c.2420G>A;c.2395delT;c.2246T>C;c.2243G>C;c.2209G>C;c.2125C>T;c.1943C>G;c.1880G>A;c.1879C>T;c.1789C>T;c.1763G>A;c.1760C>T;c.1754G>A;c.1716G>A;c.1646delT;c.1437C>G;c.1433+1G>A;c.1399G>A;c.1270_1271delCT;c.1120C>T;c.1073delA;c.1024-1G>C;c.926G>A;c.925C>T;c.922C>T;c.911T>G;c.823C>T;c.752C>T;c.695G>A;c.679C>T;c.409C>T;c.380_386delTGCCGCC;c.264C>G;c.202C>T;c.160C>T

Muscular dystrophy-dystroglycanopathy, type 3A (Walker-Warburg syndrome); Type 3B; Type 3C (limb-girdle muscular dystrophy, type 15 [LGMDR15])

Descripción enfermedad:
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies) type A3 which includes both the more severe Walker-Warburg syndrome (WWS) and the slightly less severe muscle-eye-brain disease (MEB), follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the POMGNT1 gene located on chromosomal region 1p34.1. The age of onset is infantile. This disease is characterized by generalized severe hypotonia, muscle weakness, absent psychomotor development, eye involvement and seizures. The prevalence is 1-9:100,000.

c.1902delT;c.1879delG;c.1870-1G>C;c.1829+1G>A;c.1829+1G>C;c.1829+1G>T;c.1829C>G;c.1810delG;c.1864delC;c.1852A>T;c.1832delT;c.1814G>A;c.1814G>C;c.1786-1G>A;c.1786-2A>G;c.1785+2T>G;c.1769G>A;c.1741_1745delATGGA;c.1738C>T;c.1719delC;c.1695_1698delTTTC;c.1694_1695delCT;c.1649+2T>G;c.1649G>A;c.1605-1G>C;c.1604+2T>C;c.1604+1G>A;c.1562delA;c.1545delC;c.1540-2A>G;c.1538_1539+2delACGT;c.1539+1G>A;c.1539+1G>T;c.1505G>C;c.1490G>A;c.1478C>G;c.1469G>A;c.1425G>A;c.1413+1G>A;c.1413+1G>C;c.1413+1G>T;c.1411A>T;c.1350_1354delCTGGG;c.1342G>C;c.1324C>T;c.1319T>G;c.1285-2A>G;c.1274G>C;c.1212-1G>C;c.1152+2T>C;c.1113delC;c.1104_1105delGT;c.1011dupT;c.987delT;c.982dupG;c.932G>A;c.931C>T;c.880-1G>A;c.880-2A>G;c.879+2T>C;c.879+1G>C;c.875delA;c.794G>A;c.653-2A>C;c.652+1G>A;c.643C>T;c.636C>T;c.593delG;c.594C>G;c.478delA;c.458C>G;c.447delT;c.354+1G>A;c.351delC;c.314C>G;c.236-1G>T;c.233_234delAT;c.187C>T;c.185_186insA;c.121-2A>G;c.92dupA;c.25dupC

Muscular dystrophy-dystroglycanopathy, type 1A (Walker-Warburg syndrome); Type 1B; Type 1C (limb-girdle muscular dystrophy, type 11 [LGMD R11])

Descripción enfermedad:
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type 1A follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the POMT1 gene located on chromosomal region 9q34.13. Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A), which includes both the more severe Walker-Warburg syndrome (WWS) and the slightly less severe muscle-eye-brain disease (MEB), is a genetically heterogeneous disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and early death. The phenotype commonly includes cobblestone (type II) lissencephaly, cerebellar malformations, and retinal malformations. Congenital muscular dystrophy-dystroglycanopathies with or without mental retardation (type 1B) represent the intermediate range of the spectrum of dystroglycanopathies. The muscular dystrophy-dystroglycanopathy type 1C (limb-girdle phenotype) is characterized by onset of muscular weakness apparent after ambulation is achieved; mental retardation and mild brain anomalies are variable (Balci et al., 2005; review by Godfrey et al., 2007).

c.132A>C;c.193G>A;c.226G>A;c.428-2A>G;c.430A>G;c.558G>A;c.598G>C;c.605+1G>C;c.765+1G>A;c.793C>T;c.831C>G;c.907C>T;c.1053-2A>C;c.1056T>A;c.1081C>T;c.1153C>T;c.1241C>T;c.1242-2A>G;c.1261dupC;c.1261_1262delCT;c.1276C>T;c.1280_1281delAGinsTC;c.1338+2T>C;c.1427T>G;c.1540C>T;c.1544dupA;c.1545C>G;c.1723delC;c.1746G>C;c.1770G>C;c.1858C>T;c.1864C>T;c.1958C>T;c.2005G>A;c.2070-1G>C;c.2110dupG;c.2163C>A;c.2167dupG;c.2179_2180delTC

Muscular dystrophy-dystroglycanopathy, type 2A (Walker-Warburg syndrome); Type 2B; Type 2C (limb-girdle muscular dystrophy, type 14 [LGMD R14])

Descripción enfermedad:
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the POMT2 gene located on chromosomal region 14q24.3. Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A), which includes both the more severe Walker-Warburg syndrome (WWS) and the slightly less severe muscle-eye-brain disease (MEB), is a genetically heterogeneous disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and early death. The phenotype commonly includes cobblestone (type II) lissencephaly, cerebellar malformations, and retinal malformations. MD Type 2B is associated with mental retardation and mild structural brain abnormalities. Type 2C has an onset after ambulation is achieved. Cognition is normal.

c.2243G>C;c.2177G>A;c.1997A>G;c.1941G>A;c.1912C>T;c.1762C>T;c.1726-2A>G;c.1658dupA;c.1608_1609delCA;c.1603delC;c.1484+1G>T;c.1445G>T;c.1417C>T;c.1261delC;c.1123_1124dupAC;c.1117G>T;c.1057G>A;c.1045_1052delCGGATGGCinsG;c.1006+5G>A;c.1006+1G>A;c.958C>T;c.924-2A>C;c.924-2A>G;c.881A>G;c.737G>A;c.678delG;c.639C>A;c.551C>T;c.462G>A;c.431T>G;c.248+2T>C;c.248+1G>C

Pituitary hormone deficiency, combined, type 1

Descripción enfermedad:
Pituitary hormone deficiency, combined, type 1 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the POU1F1 gene located on chromosomal region 3p11.2. The age of onset is early. This disease is characterized by short stature, cognitive alterations or delayed puberty. The prevalence is 1:8,000.

c.853dupA;c.825delA;c.826G>T;c.793C>T;c.766G>A;c.743+1G>T;c.716_720delGGAAA;c.655T>C;c.615C>G;c.593G>A;c.592C>T;c.550G>C;c.511A>T;c.506G>A;c.482T>G;c.469G>T;c.71C>T

Ceroid lipofuscinosis, neuronal, type 1

Descripción enfermedad:
Neuronal ceroid lipofuscinoses, type 1 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the PPT1 gene located on chromosomal region 1p32. The age of onset is adult. This disease is characterized by dementia, seizures and loss of motor capacities, and sometimes associated with visual loss caused by retinal degeneration. The prevalence is 1.5:1,000,000-9:1,000,000.

c.914T>C;c.888G>A;c.886T>C;c.871C>T;c.840dupA;c.799-2A>G;c.798+2T>C;c.798+1G>T;c.776dupA;c.774dupA;c.749G>T;c.739T>C;c.727-2A>T;c.713C>T;c.707T>A;c.683T>G;c.674T>C;c.665T>C;c.656T>A;c.653dupA;c.644delA;c.628-1G>T;c.627+1G>T;c.566C>G;c.560A>G;c.558G>A;c.550G>A;c.544C>T;c.541G>A;c.541G>T;c.538dupC;c.536+2T>C;c.536+1G>A;c.532delG;c.529C>G;c.529C>T;c.490C>T;c.455delG;c.456C>A;c.455G>A;c.451C>T;c.433+1G>A;c.424C>T;c.398delT;c.364A>T;c.363-2A>G;c.362+1G>A;c.327C>A;c.325T>G;c.322G>C;c.310A>T;c.294_297dupACTT;c.281_282delCA;c.236A>G;c.234+1G>A;c.223A>C;c.184delA;c.175delG;c.169dupA;c.163A>T;c.134G>A;c.133T>C;c.125G>A;c.125-2A>G;c.124+2T>A;c.124+1G>A;c.114delG;c.114G>A;c.114G>T;c.29T>A;c.3G>A

Hemophagocytic lymphohistiocytosis, familial, type 2

Descripción enfermedad:
Familial hemophagocytic lymphohistiocytosis, type 2 (FHL2) is an autosomal recessive disorder of immune dysregulation with onset in infancy or early childhood. It is characterized clinically by fever, edema, hepatosplenomegaly, and liver dysfunction. Neurologic impairment, seizures, and ataxia are frequent. Laboratory studies show pancytopenia, coagulation abnormalities, hypofibrinogenemia, and hypertriglyceridemia. There is increased production of cytokines, such as gamma-interferon (IFNG; 147570) and TNF-alpha (191160), by hyperactivation and proliferation of T cells and macrophages. Activity of cytotoxic T cells and NK cells is reduced, consistent with a defect in cellular cytotoxicity. Bone marrow, lymph nodes, spleen, and liver show features of hemophagocytosis. Chemotherapy and/or immunosuppressant therapy may result in symptomatic remission, but the disorder is fatal without bone marrow transplantation (Dufourcq-Lagelouse et al., 1999; Stepp et al., 1999; Molleran Lee et al., 2004).

c.1385C>A;c.1286G>A;c.1246C>T;c.1122G>A;c.1120T>G;c.1090_1091delCT;c.1034C>T;c.836G>A;c.673C>T;c.666C>A;c.548T>G;c.207delC;c.190C>T;c.50delT

Pituitary hormone deficiency, combined, type 2

Descripción enfermedad:
Pituitary hormone deficiency, combined, type 2, genetic forms follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the PROP1 gene located on chromosomal region 5q35.3. The age of onset is early. This disease is characterized by short stature, cognitive alterations or delayed puberty.

c.582G>A;c.469dupT;c.359G>A;c.358C>T;c.349T>A;c.343-2A>T;c.342+1G>A;c.340C>T;c.334C>T;c.310delC;c.301_302delAG;c.295C>T;c.288_289delCT;c.274C>T;c.263T>C;c.247C>T;c.218G>A;c.217C>T;c.197dupC;c.191dupG;c.157delA;c.150_151delAG;c.150delA;c.112_124delTCGAGTGCTCCAC;c.110-2A>G;c.4delG;c.2T>C

Combined SAP deficiency

Descripción enfermedad:
Combined saposin (SAP) deficiency follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the PSAP gene located on chromosomal region 10q22.1. The age of onset is neonatal/infancy. This disease is characterized by hypotonia, massive myoclonic bursts, abnormal ocular movements and dystonia. Grand mal seizures and seizures triggered by tactile stimuli have been described. Patients also develop hepatosplenomegaly. Death between 1 and 4 months usually occurs from respiratory failure following repeated pulmonary infections. The prevalence is below 1/1,000,000.

c.1297C>T;c.1154G>T;c.1153T>G;c.1055T>C;c.722G>C;c.650C>T;c.643A>C;c.607C>T;c.1A>T

Hyperphenylalaninemia, BH4-deficient, type A

Descripción enfermedad:
Tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia (HPA) comprises a genetically heterogeneous group of progressive neurologic disorders caused by autosomal recessive mutations in the genes encoding enzymes involved in the synthesis or regeneration of BH4. BH4 is a cofactor for phenylalanine hydroxylase (PAH; 612349), tyrosine hydroxylase (TH; 191290) and tryptophan hydroxylase (TPH1; 191060), the latter 2 of which are involved in neurotransmitter synthesis. The BH4-deficient HPAs are characterized phenotypically by hyperphenylalaninemia, depletion of the neurotransmitters dopamine and serotonin, and progressive cognitive and motor deficits (Dudesek et al., 2001). HPABH4A, caused by mutations in the PTS gene, represents the most common cause of BH4-deficient hyperphenylalaninemia (Dudesek et al., 2001). Other forms of BH4-deficient HPA include HPABH4B (233910), caused by mutation in the GCH1 gene (600225), HPABH4C (261630), caused by mutation in the QDPR gene (612676), and HPABH4D (264070), caused by mutation in the PCBD1 gene (126090). Niederwieser et al. (1982) noted that about 1 to 3% of patients with hyperphenylalaninemia have one of these BH4-deficient forms. These disorders are clinically and genetically distinct from classic phenylketonuria (PKU; 261600), caused by mutation in the PAH gene.Two additional disorders associated with BH4 deficiency and neurologic symptoms do not have overt hyperphenylalaninemia as a feature: dopa-responsive dystonia (612716), caused by mutation in the SPR gene (182125), and autosomal dominant dopa-responsive dystonia (DYT5; 128230), caused by mutation in the GCH1 gene. Patients with these disorders may develop hyperphenylalaninemia when stressed.

c.73C>G;c.74G>A;c.83+1G>A;c.84-3C>G;c.118_121delTTTG;c.155A>G;c.164-2A>G;c.186+1G>T;c.200C>T;c.227_228delTC;c.244-1G>T;c.286G>A;c.297C>A;c.314+1G>C;c.315-2A>G;c.315-1G>C;c.347A>G;c.361_374delGTTCTTCCTGTAGG;c.393delA

McArdle disease

Descripción enfermedad:
McArdle disease follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the PYGM gene located on chromosomal region 11q13.1. The age of onset is infantile. This disease is characterized by muscular exercise intolerance with myalgia, cramps, fatigue, and muscle weakness.

c.2392T>C;c.2380-1G>A;c.2352C>A;c.2312G>A;c.2262delA;c.2231_2244delAGCAGCTGAGCAGT;c.2178-1G>A;c.2136dupT;c.2128_2130delTTC;c.1970-1G>A;c.1970-2A>T;c.1969+1G>T;c.1963G>A;c.1948C>T;c.1827+1G>C;c.1827G>A;c.1797delT;c.1768+2T>G;c.1768+1G>A;c.1725delA;c.1726C>T;c.1722T>G;c.1717G>T;c.1680delC;c.1628A>C;c.1621G>T;c.1527_1530delGGAGinsTGA;c.1466dupC;c.1466C>G;c.1366G>A;c.1239+1G>A;c.1093-1G>T;c.1092+1G>A;c.808C>T;c.660+1G>A;c.613G>A;c.528+2T>G;c.501dupT;c.445_448delGCAA;c.425-2A>G;c.425-26A>G;c.407delG;c.393delG;c.370G>T;c.280C>T;c.262_263delTT;c.251_261delACTACCTGTCT;c.255C>A;c.253delT;c.252C>G;c.148C>T;c.78_79delTG;c.13_14delCT;c.1A>C;c.1A>G

Hyperphenylalaninemia, BH4-deficient, type C

Descripción enfermedad:
Hyperphenylalaninemia, BH4-deficient, type C (HPABH4C) is a are autosomal recessive disorder characterized by hyperphenylalaninemia and severe neurologic symptoms (malignant hyperphenylalaninemia) including axial hypotonia and truncal hypertonia, abnormal thermogenesis, and microcephaly. These signs are attributable to depletion of the neurotransmitters dopamine and serotonin, whose syntheses are controlled by tryptophan and tyrosine hydroxylases that use BH-4 as cofactor. Patients do not respond to phenylalanine-restricted diet. HPABH4C is lethal if untreated.

c.472C>T;c.449A>G;c.344C>T;c.322T>G;c.270G>A;c.106T>C;c.68G>A;c.44T>C

Carpenter syndrome

Descripción enfermedad:
Carpenter syndrome follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the RAB23 gene located on chromosomal region 6p11.2. The age of onset is early. This disease is characterized by acrocephaly, peculiar facies, brachydactyly and syndactyly in the hands, and preaxial polydactyly and syndactyly of the toes. The prevalence is <1:1,000,000.

c.481G>C;c.434T>A;c.407dupC;c.82C>T

Omenn syndrome; Severe combined immunodeficiency, B cell-negative

Descripción enfermedad:
Omenn syndrome follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the RAG1 and RAG2 genes located on chromosomal region 11p12. The age of onset is early. This disease is characterized by erythroderma, desquamation, alopecia, chronic diarrhea, failure to thrive, lymphadenopathy, and hepatosplenomegaly, associated with severe combined immunodeficiency.
Severe combined immunodeficiency, autosomal recessive, T cell-negative (T-), B cell negative (B-), NK cell positive (NK+) is also caused by mutation in the RAG1 and RAG2 genes. This disease is characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. Without treatment, patients usually die within the first year of life.

c.256_257delAA;c.322C>T;c.335G>A;c.555delG;c.775delA;c.940C>T;c.983G>A;c.999T>A;c.1186C>T;c.1187G>A;c.1286A>G;c.1566G>T;c.1681C>T;c.1682G>A;c.2005G>A;c.2164G>A;c.2210G>A;c.2320G>T;c.2326C>T;c.2333G>A;c.2689C>T;c.2814T>G;c.2923C>T;c.2974A>G

Omenn syndrome; Severe combined immunodeficiency, B cell-negative

Descripción enfermedad:
Omenn syndrome follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the RAG1 and RAG2 genes located on chromosomal region 11p12. The age of onset is early. This disease is characterized by erythroderma, desquamation, alopecia, chronic diarrhea, failure to thrive, lymphadenopathy, and hepatosplenomegaly, associated with severe combined immunodeficiency.
Severe combined immunodeficiency, autosomal recessive, T cell-negative (T-), B cell negative (B-), NK cell positive (NK+) is also caused by mutation in the RAG1 and RAG2 genes. This disease is characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. Without treatment, patients usually die within the first year of life.

c.1403_1406delATCT;c.1352G>C;c.854T>G;c.601C>T;c.547T>C;c.539C>A;c.518A>G;c.374_375delCA;c.283G>A;c.230C>A;c.218G>A;c.217C>T;c.193G>T;c.123C>G;c.115A>G;c.104G>T

Fetal akinesia deformation sequence; Myasthenic syndrome, congenital, 11, associated with AChR deficiency

Descripción enfermedad:
Fetal akinesia deformation sequence follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the RAPSN gene located on chromosomal region 11p11.2. The age of onset is early. This disease is characterized by multiple joint contractures, facial anomalies and pulmonary hypoplasia. The prevalence is 1:3,000. Congenital myasthenic syndrome associated with AChR deficiency is a disorder of the postsynaptic neuromuscular junction (NMJ) clinically characterized by early-onset muscle weakness with variable severity.

c.1177_1178delAA;c.1083_1084dupCT;c.853C>T;c.848T>C;c.807C>A;c.737C>T;c.566C>T;c.549_553dupGTTCT;c.490C>T;c.484G>A;c.416T>C;c.370C>T;c.264C>A;c.133G>A;c.41T>C

Leber congenital amaurosis, type 13

Descripción enfermedad:
Leber congenital amaurosis type 13 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the RDH12 gene located on chromosomal region 14q24.1. The age of onset is early. This disease is characterized by blindness, nystagmus, roving eye movement and lack of detectable signals on an electroretinogram, leading to severe visual impairment within the first year of life.

c.63_66delCATC;c.146C>T;c.152T>A;c.184C>T;c.210dupC;c.250C>T;c.295C>A;c.377C>T;c.379G>T;c.451C>A;c.451C>G;c.464C>T;c.523T>C;c.565C>T;c.658+1G>A;c.677A>G;c.688C>G;c.778delG;c.806_810delCCCTG

Leber congenital amaurosis, type 2

Descripción enfermedad:
Leber congenital amaurosis 2 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the RPE65 gene located on chromosomal region 1p31.3-p31.2. The age of onset is variable. This disease is characterized by a severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.

c.1543C>T;c.1366delG;c.1355T>G;c.1338+1G>A;c.1292A>G;c.1102T>C;c.1087C>A;c.1067delA;c.1022T>C;c.907A>T;c.893delA;c.700C>T;c.514_515delGT;c.370C>T;c.304G>T;c.271C>T;c.149_150delTT;c.130C>T;c.95-2A>T;c.11+5G>A

Joubert syndrome, type 7; Meckel syndrome, type 5; COACH syndrome

Descripción enfermedad:
Joubert syndrome (JBTS) type 7 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the RPGRIP1L gene located on chromosomal region 16q12.2. The age of onset is early. JBTS is characterized by congenital malformation of the brainstem and agenesis of the cerebellar vermis (molar tooth sign) leading to an abnormal respiratory pattern, nystagmus, hypotonia, mental retardation, ataxia, and delay in achieving motor milestones. Other variable features include retinal dystrophy (less common in JBTS7) and nephronophthisis (usually juvenile). The prevalence is 1:100,000. RPGRIP1L gene is also associated with Meckel syndrome type 5, a rare, autosomal recessive lethal condition characterized by central nervous system malformations, postaxial, polydactyly, multicystic kidney dysplasia, and ductal proliferation in the portal area of the liver. Other phenotype associated is COACH syndrome, an autosomal recessive disorder characterized by mental retardation, ataxia due to cerebellar hypoplasia, and hepatic fibrosis. Other features, such as coloboma and renal cysts, may be variable. COACH syndrome is considered by some to be a subtype of Joubert syndrome with congenital hepatic fibrosis.

c.3701+1G>T;c.3634_3637delGAAA;c.3529C>T;c.3299_3300dupTC;c.3187G>T;c.2794_2795delTT;c.2614C>T;c.2413C>T;c.2305-1G>A;c.2299C>T;c.2269delA;c.2200C>T;c.2083G>C;c.2050C>T;c.1975T>C;c.1843A>C;c.1829A>C;c.1721delA;c.1709dupA;c.1700-1G>A;c.1489G>T;c.1421delA;c.1326_1329delAAAA;c.1329dupA;c.1243+1G>A;c.1158dupA;c.1132delT;c.1120delC;c.1033C>T;c.776+1G>A;c.757C>T;c.723_726delTGAA;c.697A>T;c.394A>T;c.230+1G>A;c.118C>T

Dyskeratosis congenita, autosomal recessive 5

Descripción enfermedad:
Dyskeratosis congenita (DKC) is a bone marrow failure syndrome characterized by severely shortened telomeres and diverse clinical symptoms. The classic presentation of DKC includes nail dystrophy, abnormal skin pigmentation, and oral leukoplakia. Hoyeraal-Hreidarsson syndrome (HHS) is a severe clinical variant of DKC that is characterized by intrauterine growth failure, microcephaly, developmental delay, immunodeficiency, bone marrow failure, and cerebellar hypoplasia. Patients with mutations in the RTEL1 gene tend to present with HHS (summary by Walne et al., 2013).

c.49C>T;c.102+2T>C;c.388_389delTC;c.442C>T;c.458_459delAA;c.525C>A;c.535G>T;c.602delG;c.630C>A;c.649C>T;c.751G>A;c.897delC;c.958+2dupT;c.1037+1G>T;c.1135+1G>A;c.1451C>T;c.1476G>T;c.1482-1G>A;c.1546G>C;c.1596-1G>A;c.1618T>G;c.1648C>T;c.1773G>T;c.1861G>A;c.2005C>T;c.2021dupG;c.2097C>G;c.2216G>T;c.2219_2227delATGTCATCC;c.2233G>A;c.2260C>T;c.2265+2T>A;c.2413+1G>C;c.2414-2A>G;c.2587_2590delTCTG;c.2653-2A>C;c.2851+1G>T;c.2869C>T;c.2881A>T;c.2920C>T;c.2956C>T;c.3104dupC;c.3110-2A>C;c.3110-2A>T;c.3334delC;c.3344-2A>G;c.3370delC;c.3371A>C;c.3376C>T;c.3559C>T;c.3791G>A

Spastic ataxia, Charlevoix-Saguenay, type

Descripción enfermedad:
Spastic ataxia, Charlevoix-Saguenay type follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the SACS gene located on chromosomal region 13q11. The age of onset is early. This disease is characterized by early-onset cerebellar ataxia with spasticity, a pyramidal syndrome and peripheral neuropathy. The prevalence is 1:1,500-1:2,000.

c.13237C>T;c.13132C>T;c.12973C>T;c.12851_12854delAGAG;c.12232C>T;c.12160C>T;c.12028C>T;c.11707C>T;c.11374C>T;c.11265_11266delAT;c.11185C>T;c.10906C>T;c.10466_10467delCT;c.9508C>T;c.8844delT;c.8793delA;c.8393C>A;c.7504C>T;c.7276C>T;c.7162_7163delAC;c.6563T>A;c.6409C>T;c.6355C>T;c.6172delT;c.5764_5767delTTAC;c.5719C>T;c.5618_5619delAT;c.5151dupA;c.5125C>T;c.4933C>T;c.4744G>A;c.4593dupA;c.4033dupC;c.3328dupA;c.3198T>A;c.2903_2906delACAG;c.2439_2440delAT;c.2224C>T;c.2186-2A>G;c.2182C>T;c.2076delC;c.1919_1920delAC;c.1706G>A;c.1681delG;c.1672C>T;c.1607C>T;c.1276_1277dupTT;c.1228_1229delTT;c.1189_1190delAG;c.1137dupA;c.1085delA;c.994A>T;c.961C>T;c.832C>T;c.814C>T;c.712A>T;c.605-1G>A;c.604+1G>A;c.517C>T;c.468_469insG;c.262C>T;c.29delC

Shwachman-Diamond syndrome

Descripción enfermedad:
Shwachman-Diamond syndrome follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the SBDS gene located on chromosomal region 7q11.21. The age of onset is infantile. This disease is characterized by chronic and usually mild neutropenia, pancreatic exocrine insufficiency associated with steatorrhea and growth failure, skeletal dysplasia with short stature, and an increased risk of bone marrow aplasia or leukemic transformation, cutaneous (eczema or ichthyosis) and dental anomalies, and psychomotor retardation. The prevalence is 1:76,000 newborn.

c.652C>T;c.624+1G>C;c.523C>T;c.377G>C;c.297_300delAAGA;c.258+2T>C;c.258+1G>C;c.183_184delTAinsCT;c.184A>T;c.120delG;c.95A>G;c.41A>G;c.13delA

Limb-girdle muscular dystrophy, type 3 (LGMD R3)

Descripción enfermedad:
Autosomal recessive limb-girdle muscular dystrophy type 3 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the SGCA gene located on chromosomal region 4q12. The age of onset is variable. This disease is characterized by limb-girdle weakness and calf pseudohypertrophy. The prevalence is 1:1,000,000-9:1,000,000.

c.-1_9delCATGGCTGAG;c.100C>T;c.101G>A;c.158-2A>G;c.161delT;c.183dupC;c.220delC;c.229C>T;c.292C>T;c.293G>A;c.313_319delGTCACAG;c.313-2A>G;c.322_325dupTACA;c.348_352dupTCGGC;c.371T>C;c.391delC;c.403C>T;c.409G>A;c.464delG;c.480_481delCT;c.488dupG;c.489delA;c.511C>T;c.518T>C;c.530delC;c.559delC;c.574C>T;c.580G>T;c.585-2A>C;c.585-2A>T;c.585-1G>A;c.585-1G>C;c.614C>A;c.676C>T;c.739G>A;c.747+1G>A;c.748-2A>T;c.754_755delAA;c.755delA;c.770delC;c.846_847delAGinsT;c.850C>T;c.892delC;c.903_904dupCC;c.949G>T;c.981_982dupCG;c.1054G>T

Limb-girdle muscular dystrophy, type 4 (LGMD R4)

Descripción enfermedad:
Autosomal recessive limb-girdle muscular dystrophy type 4 follows an autosomal recessive pattern of inheritance and is caused by pathogenic variants in the SGCB gene located on chromosomal region 4q12. The age of onset is variable. This disease is characterized by limb-girdle weakness, particularly of the pelvic girdle muscles.