Genetic and Structural Variations in Czech Patients With Congenital Myopathies.

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.