improved diagnostic yield of neuromuscular disorders applying clinical exome sequencing (ces) in patients arising from a consanguineous population

neuromuscular disorders (nmds) include a broad range of diseases affecting muscles, nerves and neuromuscular junctions. approximately 761 different disorders occur in this group which is subdivided into 16 different subgroups with 406 known genes. nmds are genetically and clinically heterogeneous conditions. the advent of next generation sequencing (ngs) approaches has accelerated the pace of discovery of nmds genes. in this study, we describe the validation of an ngs panel, for comprehensive mutation detection in nmds patients. during a year, a total of 46 patients were examined, mostly offspring of consanguineous marriages. data analysis was performed to identify the most probable pathogenic rare variants in known nmd genes. co-segregation analysis and genotype–phenotype correlation led to identification of causal variants. in 33 out of 46 patients (71.7%), the pathogenic variant was identified in the following known genes: capn3, col6a1, col6a3, dmd, dysf, fhl1, gjb1, ispd, lama2, lmna, plec1, ryr1, sgca, sgcb, syne1, tnnt1 and 22 novel pathogenic variants were detected which is quite high compared to the overall diagnostic yield of no more than 50% in most other reports.