Genetic and Structural Variations in Czech Patients With Congenital Myopathies

Area of Science:

• Genetics
• Neuromuscular Disorders
• Molecular Biology

Background:

• Congenital myopathies (CMs) are a diverse group of genetic muscle disorders.
• They cause hypotonia and muscle weakness, with over 41 known causative genes.
• CMs exhibit various inheritance patterns, including autosomal dominant, recessive, and X-linked.

Purpose of the Study:

• To genetically characterize a cohort of 79 unrelated congenital myopathy patients.
• To identify novel pathogenic variants and understand mutational mechanisms in CMs.
• To investigate large gene deletions and their impact on genomic instability.

Main Methods:

• Next-generation sequencing (NGS) was employed for genetic analysis.
• Analysis included identification and characterization of mutant alleles and variants.
• Breakpoint junction sequencing was performed for large deletions in NEB and RYR1 genes.

Main Results:

• A total of 113 mutant alleles and 97 presumed pathogenic variants were identified.
• 54 variants were found to be exclusive to the Czech CM population.
• Large deletions were detected in MTM1, NEB, and RYR1 genes, with a novel dominant NEB deletion reported in one family.

Conclusions:

• The study expands the spectrum of known genetic variants in congenital myopathies.
• Insights into mechanisms of genomic instability and structural variations were gained.
• Findings contribute to a better understanding of neuromuscular diseases and their genetic underpinnings.