Genetic investigation of Nemaline myopathy in Middle Eastern patients

Background: Nemaline myopathy is a rare genetic muscular disease clinically characterized by muscle weakness and hypotonia, with nemaline rods in skeletal muscle fibers. Nemaline myopathy is both genetically and phenotypically heterogeneous disease, for which a number of disease genes have been identified. This research were conducted with the aim of determining the role of Genetic investigation of Nemaline myopathy in Middle Eastern patients.Methods: We investigated the clinical features and genetic cause of nemaline myopathy in pathologically diagnosed patients from Middle Eastern families. Half of the families were consanguineous (first-cousins). We applied a targeted next-generation sequencing (NGS) myopathy panel to identify single nucleotide variants (SNVs),insertions/deletions, and copy number variations in these patients. In addition, we reviewed the previously reported cases with the identified variants and attempted to suggest genotype–phenotype correlations. Results: Sequence analysis revealed rare homozygous SNVs in NEB (in 66% of families) and ACTA1 (in 34% of families). Segregation analysis showed that the other affected family members were homozygous for the identified variants, whereas parents were heterozygous and healthy siblings were either heterozygous or wild type. All NEB variants were predicted to cause loss of function of the gene products, whereas the ACTA1 variants were missense. Five of the identified disease-causing variants were novel. Conclusion: These results suggest a) NEB and ACTA1 to be the most prevalent cause of nemaline myopathy in Middle Eastern patients, and b) targeted NGS panel is a rapid and cost-effective approach to analyze the molecular basis of nemaline myopathy.

کلیدواژه ها:

Nemaline myopathy ، NEB ، ACTA1