Utility of next-generation sequencing in the diagnosis of neurological disorders

Background: The spectrum of neurological diseases encompasses a large number of disorders, including neuromuscular disorder (NMDs), ataxias, and muscular dystrophies. A detailed clinical examination, followed by electromyography and muscle biopsy, is a traditional diagnostic approach. However, it is never helpful in the identification of the subgroups of either neuropathies or muscular dystrophies apart from being a painful procedure. Aim: The present study was to assess the diagnostic yield of next-generation sequencing (NGS) in the diagnosis of neurological disorders. Materials and Methods: It was a cross-sectional study where consecutive neurological patients for whom NGS was done were included. These variants were classified as pathogenic/likely pathogenic, variants of uncertain significance (VUS), likely benign and benign. Results: Among the 45 cases included, 31 variants were identified in 30 genes, and in 15 patients, no variants were detected. Among 31 variants, 14 were previously reported for the causal of neurological disorder, including NMD, whereas 16 were novel variants (14 missense, 1 frameshift, and 1 splice donor). A definite molecular diagnosis was achieved in 21 cases that were either pathogenic/likely pathogenic, whereas 9 came to be VUS; however, the clinical manifestations correlated well. The phenotype-based sequencing showed a high diagnostic yield of 66% in the present study. Conclusion: NGS improves diagnostic efficiency with quicker and earlier diagnosis. In addition, it is a reliable and noninvasive technique that is effective in the detection of single nucleotide polymorphisms and small deletions.