The applications and challenges of next- generation sequencing in diagnosing neuromuscular disorders

Inherited neuromuscular disorders (NMDs) form a group of highly heterogeneous diseases with a relatively high incidence of 1 in 3000. NMDs affect the peripheral nervous and muscular systems, resulting in gross motor disability. Disease subtype diagnosis is complicated by the high clinical and genetic heteroge- neities of the disease and consequently more than 50% of the cases remain molecu- larly uncharacterized. Traditional gene-by-gene approach is quite exhaustive and after a few negative tests the quest for diagnosis is often given up without establish- ing diagnosis. However in the recent years, the clinical applications of next- generation sequencing (NGS)-based comprehensive approach such as multi-gene panels, and exome sequencing have allowed for rapid diagnosis. Additionally, its applications in research settings have allowed for identification of new disease- causing genes and variants which translated into an improved clinical diagnostic yield. Here, we discuss the application of NGS technology in NMDs as a diagnostic and research tool. We conclude that such an application will tremendously broaden our knowledge of NMDs; the outcome of which includes rapid and accurate diagnosis that would result in an earlier and more effective intervention.