Klinische FragestellungHT amedes STANDARD Heterozygotie-Test

NGS + X

Auf der Grundlage fachlicher Empfehlungen (1) bietet amedes ein NGS-Panel zur Erfassung von pathogenen Varianten an, die mit autosomal-rezessiven und X-gebundenen Krankheiten assoziiert sind. Es umfasst 113 Gene und die damit assoziierten Erbkrankheiten. Der cut-off-Wert für einen Einschluss liegt bei einer Heterozgyten-Frequenz von ≥ 1:200 für autosomal-rezessive Erkrankungen (bezogen auf mindestens eine US-amerikanische Subpopulation (1)). Die kumulative Entdeckungswahrscheinlichkeit für mindestens eine pathogene Variante in Individuen bzw. Paaren (= Paaren mit pathogenen Varianten in mindestens einem gleichen Gen) hängt in hohem Maße von der Ethnizität und dem Verwandtschaftsgrad von Paaren ab (2). Sie bewegt sich zwischen 19,9% und 51,0% für Individuen bzw. 0,3% und 17,2% für Paare mit unterschiedlichem Verwandtschaftsgrad.

Entdeckungswahrscheinlichkeit für individuelle Genträgerschaft und Genträgerschaft bei Paaren, nach Ethnizität und Verwandtschaftsgrad (autosomal-rezessive Krankheiten)

AFR: Afrikaner, AMR: American Hispanics, EAS: Ostasiaten, SAS: Südasiaten, NFE: Europäer außer Finnland, ASJ: Ashkenazi Juden

Verwandtschaftskoeffizienten bei Paaren: 1/4 = Onkel-Nichte und Tante-Neffe; 1/8 = Cousin-Cousine 1. Grades; 1/32 = Cousin-Cousine 2. Grades

Referenzen:

(1) Gregg et al.; PMID: 34285390

(2) Schmidtke and Krawczak; PMID: 35661981

• Alias: EHT
• HT ersetzt EHT
• Mutation carrier test; Carrier test
• Für konsanguine Paare aus mitteleuropäischen und anderen Bevölkerungen ...
• ...inclusive Störungen der Sensorik, Geschlechtsdifferenzierung oder geistige Entwicklung
• 3-methylcrotonyl CoA carboxylase 2 deficiency (MCCC2)
• AR polycystic kidney disease (PKHD1)
• Achondrogenesis Ib (SLC26A2)
• Achromatopsia 3 (CNGB3)
• Adrenal hypoplasia, congenital (NR0B1)
• Adrenal insufficiency, congenital, with 46XY sex reversal, partial or complete (CYP11A1)
• Adrenoleukodystrophy (ABCD1)
• Aicardi Goutieres syndrome 2 (RNASEH2B)
• Argininosuccinate aciduria (ASL)
• Aspartylglucosaminuria (AGA)
• Atransferrinemia (TF)
• Autoimmune polyendocrinopathy syndrome type I (AIRE)
• Bardet–Biedl syndrome 1 (BBS1)
• Bardet–Biedl syndrome 2 (BBS2)
• Basal ganglia disease, biotin-responsive (SLC19A3)
• Biotinidase deficiency (BTD)
• Bloom syndrome (BLM)
• Canavan disease (ASPA)
• Carbohydrate-deficient glycoprotein syndrome type Ia (PMM2)
• Cardiomyopathy, dilated, 1X (FKTN)
• Carnitine palmitoyltransferase II deficiency, infantile (CPT2)
• Carnitine palmitoyltransferase II deficiency, lethal neonatal (CPT2)
• Cerebral creatine deficiency syndrome 1 (SLC6A8)
• Cerebrooculofacioskeletal syndrome 2 (ERCC2)
• Cerebrotendinous xanthomatosis (CYP27A1)
• Chondroectodermal dysplasia (EVC2)
• Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CYP21A2)
• Congenital disorder of glycosylation type 1 (DHDDS)
• Congenital hydrocephalus 1 (CCDC88C)
• Congenital myotonia, AR form (CLCN1)
• Cystic fibrosis (CFTR)
• Deafness AR 4 (SLC26A4)
• Deafness, AR 23 (PCDH15)
• Developmental and epileptic encephalopathy 1 (ARX)
• Diabetes mellitus, permanent neonatal 3 (ABCC8)
• Dihydrolipoamide dehydrogenase deficiency (DLD)
• Donnai–Barrow syndrome (LRP2)
• Ehlers–Danlos-like syndrome due to tenascin-X deficiency (TNXB)
• Epiphyseal dysplasia, multiple, 4 (SLC26A2)
• Fabry disease (GLA)
• Familial dysautonomia (ELP1)
• Fanconi anemia, complementation group C (FANCC)
• Finnish congenital nephrotic syndrome (NPHS1)
• Fragile X syndrome (FMR1)
• Fraser syndrome (GRIP1)
• Friedreich ataxia (FXN)
• GBE1-related disorders (GBE)
• Galactosemia (GALT)
• Gaucher disease, type I (GBA)
• Gaucher disease, type II (GBA)
• Glycogen storage disease Ib (SLC37A4)
• Glycogen storage disease Ic (SLC37A4)
• Glycogen storage disease type IA (G6PC1)
• Glycogen storage disease, type II, Pompe disease (GAA)
• Glycogen storage disease, type IV (GBE)
• Hemophagocytic lymphohistiocytosis, familial, 2 (PRF1)
• Hemophilia A (F8)
• Hemophilia B (F9)
• Hereditary fructosuria (ALDOB)
• Hermansky Pudlak syndrome 1 (HPS1)
• Hermansky Pudlak syndrome 3 (HPS3)
• Homocystinuria, B6 responsive + nonresponsive (CBS)
• Hydrocephalus due to congenital stenosis of aqueduct of Sylvius (L1CAM)
• Hyper-IgD syndrome (MVK)
• Hyperoxaluria, primary type I (AGXT)
• Hypophosphatasia, adult (ALPL)
• Hypophosphatasia, childhood + infantile (ALPL)
• Joubert syndrome 2 (TMEM216)
• Joubert syndrome 3 (AHI1)
• Joubert syndrome 5 (CEP290)
• Joubert syndrome 9 (CC2D2A)
• Leber congenital amaurosis 10 (CEP290)
• Macular degeneration, XL atrophic (RPGR)
• Maple syrup urine disease (BCKDHB)
• Meckel syndrome 2 (TMEM216)
• Meckel syndrome 6 (CC2D2A)
• Medium-chain acyl-coenzyme A dehydrogenase deficiency (ACADM)
• Megalencephalic leukoencephalopathy with subcortical cysts (MLC1)
• Mental retardation, XL, associated with fragile site FRAXE (AFF2)
• Metachromatic leukodystrophy (ARSA)
• Methylmalonic aciduria with homocystinuria cblC type (MMACHC)
• Methylmalonic aciduria–methylmalonyl–CoA mutase deficiency (MMUT)
• Mevalonic aciduria (MVK)
• Mitochondrial DNA depletion syndrome 4A (POLG)
• Mitochondrial DNA depletion syndrome 4B (POLG)
• Mitochondrial complex IV deficiency, nuclear type 2 (SCO2)
• Mucolipidosis type II alpha/beta (GNPTAB)
• Mucolipidosis type III alpha/beta (GNPTAB)
• Mucolipidosis type IV (MCOLN1)
• Mucopolysaccharidosis, Ich, Hurler S (IDUA)
• Mucopolysaccharidosis, Ih/s, Hurler–Scheie S (IDUA)
• Muscular dystrophy, Becker type (DMD)
• Muscular dystrophy, Duchenne type (DMD)
• Muscular dystrophy–dystroglycanopathy, type A, 5 (FKRP)
• Muscular dystrophy–dystroglycanopathy, type B, 5 (FKRP)
• Myasthenic syndrome, congenital, 4A, slow-channel (CHRNE)
• Myasthenic syndrome, congenital, 4B, fast-channel (CHRNE)
• Nemaline myopathy 2 (NEB)
• Niemann–Pick disease, type A (SMPD1)
• Niemann–Pick disease, type B (SMPD1)
• Nonsyndromic hearing loss AD 3A (GJB2)
• Nonsyndromic hearing loss AR 1A (GJB2)
• Oculocutaneous albinism brown + type II (OCA2)
• Oculocutaneous albinism type 1A + 1B (TYR)
• Opitz GBBB syndrome, type I (MID1)
• Ornithine transcarbamylase deficiency (OTC)
• Pendred syndrome (SLC26A4)
• Phenylketonuria (PAH)
• Pontocerebellar hypoplasia type 6 (RARS2)
• Primary microcephaly 1, AR (MCPH1)
• Recessive dystrophic epidermolysis bullosa (COL7A1)
• Retinitis pigmentosa 3 (RPGR)
• Retinitis pigmentosa 59 (DHDDS)
• Retinitis pigmentosa 74 (BBS2)
• Retinitis pigmentosa, XL, + sinorespiratory infections, with/-out deafness (RPGR)
• Retinoschisis 1, XL, juvenile (RS1)
• Schindler disease, type 1 (NAGA)
• Schindler disease, type 3 (NAGA)
• Short-rib thoracic dysplasia 3 with or without polydactyly (DYNC2H1)
• Sickle cell anemia β-thalassemia (HBB)
• Smith–Lemli–Opitz syndrome (DHCR7)
• Spastic paraplegia 2, XL (PLP1)
• Spinal muscular atrophy types I, II, III, IV (SMN1)
• Spinocerebellar ataxia 10 (ANO10)
• Surfactant metabolism dysfunction, pulmonary 3 (ABCA3)
• Tay–Sachs disease (HEXA)
• Trichothiodystrophy 1, photosensitive (ERCC2)
• Trimethylaminuria (FMO3)
• Tyrosinemia type I (FAH)
• Usher syndrome 3a (CLRN1)
• Usher syndrome, type 1F (PCDH15)
• Usher syndrome, type 2A (USH2A)
• Very long chain acyl-CoA dehydrogenase deficiency (ACADVL)
• Vitamin D–dependent rickets, type 1 (CYP27B1)
• Walker–Warburg congenital muscular dystrophy (FKTN)
• Wilson disease (ATP/B)
• Xeroderma pigmentosum (XPC)
• ɑ-Methylacetoacetic aciduria (ACAT1)
• ɑ-Thalassemia (HBA1)
• ɑ-Thalassemia (HBA2)