Muscular dystrophies and myopathies: the spectrum of mutated genes in the Czech Republic
Jazyk angličtina Země Dánsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
27447704
DOI
10.1111/cge.12839
Knihovny.cz E-zdroje
- Klíčová slova
- DNA diagnostics, LGMD, neuromuscular disorders, targeted next-generation sequencing,
- MeSH
- dospělí MeSH
- genetické testování * MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace MeSH
- nemoci svalů epidemiologie genetika patofyziologie MeSH
- sekvenční analýza DNA * MeSH
- svalové dystrofie epidemiologie genetika patofyziologie MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
Inherited neuromuscular disorder (NMD) is a wide term covering different genetic disorders affecting muscles, nerves, and neuromuscular junctions. Genetic and clinical heterogeneity is the main drawback in a routine gene-by-gene diagnostics. We present Czech NMD patients with a genetic cause identified using targeted next-generation sequencing (NGS) and the spectrum of these causes. Overall 167 unrelated patients presenting NMD falling into categories of muscular dystrophies, congenital muscular dystrophies, congenital myopathies, distal myopathies, and other myopathies were tested by targeted NGS of 42 known NMD-related genes. Pathogenic or probably pathogenic sequence changes were identified in 79 patients (47.3%). In total, 37 novel and 51 known disease-causing variants were detected in 23 genes. In addition, variants of uncertain significance were suspected in 7 cases (4.2%), and in 81 cases (48.5%) sequence changes associated with NMD were not found. Our results strongly indicate that for molecular diagnostics of heterogeneous disorders such as NMDs, targeted panel testing has a high-clinical yield and should therefore be the preferred first-tier approach. Further, we show that in the genetic diagnostic practice of NMDs, it is necessary to take into account different types of inheritance including the occurrence of an autosomal recessive disorder in two generations of one family.
Central European Institute of Technology Masaryk University Brno Czech Republic
Centre of Fetal Medicine and Genetics Olomouc Czech Republic
Child Neurology Thomayer's Hospital Prague Czech Republic
Department of Child Neurology University Hospital Brno Brno Czech Republic
Department of Medical Genetics Thomayer's Hospital Prague Czech Republic
Department of Neurology University Hospital Brno Brno Czech Republic
Department of Paediatrics University Hospital Olomouc Olomouc Czech Republic
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