Genetic spectrum among 2009 Iranian individuals with neuromuscular disorders using next generation sequencing and multiple ligation dependent probe amplification methods.

Hereditary neuromuscular disorders (NMDs) are clinically and genetically heterogeneous, with variable severity and onset from birth to adulthood. This study retrospectively analyzes genetic findings in 2009 Iranian individuals with suspected NMDs over 11 years to highlight gene involvement and mutational patterns. Patients underwent gene panel sequencing (GPS), whole exome sequencing (WES), or MLPA for PMP22 in cases with suspected Charcot-Marie-Tooth disease type 1 A (CMT1A). The diagnostic yield of GPS/WES was 46%. Dystrophies were the most prevalent, followed by neuropathies and myopathies. The key implicated genes were CAPN3 and DMD for dystrophies; GDAP1 and MME for neuropathies; GNE and ETFDH for myopathies. The most common phenotype group was dystrophies among both individuals with childhood-onset and adulthood-onset, but the most frequent mutated gene was CAPN3 in children and DYSF in adults. Identified variants include 761 (97%) single nucleotide variants (SNVs) and 24 (3%) copy number variations (CNVs). Notably, 26% of SNVs were novel. Among individuals tested with MLPA, 28% had confirmed PMP22 gene deletions or duplications, with 73% being duplications linked to CMT1A. This large-scale analysis provides insight into the genetic landscape of NMDs in Iran. Understanding gene distribution and mutation types can improve diagnosis and inform management strategies for affected individuals.