Genetic and Structural Variations in Czech Patients With Congenital Myopathies

Congenital myopathies (CMs) are a heterogeneous group of genetic muscle disorders characterized by hypotonia and muscle weakness, with pathogenic variants identified in at least 41 genes and inheritance patterns including autosomal dominant (AD), recessive (AR), and X-linked (XL). We present 79 unrelated patients with genetically confirmed CM using next-generation sequencing (NGS). A total of 113 mutant alleles carrying 97 different variants with a presumed pathogenic effect were identified. According to the HGMD database, 54 of these variants have been reported exclusively in the Czech CM population to date. All but five variants were small-scale. Large gene deletions were identified in the MTM1, NEB, and RYR1 genes. Sequencing of breakpoint junctions in the identified NEB and RYR1 deletions provided insights into the upstream mechanisms leading to genomic instability and resulting in structural variations. We present the family with dominant inheritance of the NEB deletion of exons 19-78. We assume that our family represents another reported case of a dominant mutation in the NEB gene. Our results contribute to further knowledge in the field of neuromuscular diseases and mutational mechanisms.

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Journal
Clinical Genetics
Published
2025-06-17
DOI
https://doi.org/10.1111/cge.14782
Citations
1
Primary Topic
Cardiomyopathy and Myosin Studies
Type
article
Field-Weighted Citation Impact
1.39

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Genetic and Structural Variations in Czech Patients With Congenital Myopathies

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Genetic and Structural Variations in Czech Patients With Congenital Myopathies

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article en
1 citations

Abstract

Congenital myopathies (CMs) are a heterogeneous group of genetic muscle disorders characterized by hypotonia and muscle weakness, with pathogenic variants identified in at least 41 genes and inheritance patterns including autosomal dominant (AD), recessive (AR), and X-linked (XL). We present 79 unrelated patients with genetically confirmed CM using next-generation sequencing (NGS). A total of 113 mutant alleles carrying 97 different variants with a presumed pathogenic effect were identified. According to the HGMD database, 54 of these variants have been reported exclusively in the Czech CM population to date. All but five variants were small-scale. Large gene deletions were identified in the MTM1, NEB, and RYR1 genes. Sequencing of breakpoint junctions in the identified NEB and RYR1 deletions provided insights into the upstream mechanisms leading to genomic instability and resulting in structural variations. We present the family with dominant inheritance of the NEB deletion of exons 19-78. We assume that our family represents another reported case of a dominant mutation in the NEB gene. Our results contribute to further knowledge in the field of neuromuscular diseases and mutational mechanisms.

Clinical GeneticsVol. 108(6)
Central European Institute of Technology (CZ), Charles University (CZ), Masaryk University (CZ), University Hospital Ostrava (CZ), Central European Institute of Technology – Masaryk University (CZ), University Hospital in Motol (CZ), University Hospital Brno (CZ), University Hospital Hradec Králové (CZ), Thomayer University Hospital (CZ), General University Hospital in Prague (CZ)
Ministerstvo Školství, Mládeže a Tělovýchovy, Agentura Pro Zdravotnický Výzkum České Republiky, European Regional Development Fund
Good health and well-being
Openalex Percentile: Top 18%
Cardiomyopathy and Myosin Studies
1.39
DOIOpen Access PDFOpenAlex
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