Identification of mutations in Korean patients with amyotrophic lateral sclerosis using multigene panel testing.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease involving motor neurons. Because a growing number of genes have been identified as the genetic etiology of ALS, simultaneous screening of mutations in multiple genes is likely to be more efficient than gene-by-gene testing. In this study, we performed a multigene panel testing by using targeted capture of 18 ALS-related genes followed by next-generation sequencing. Using this technique, we tried to identify mutations in 4 index patients with familial ALS and 148 sporadic ALS in Korean population and identified 4 known mutations in SOD1, ALS2, MAPT, and SQSTM1 genes, respectively, and 28 variants of uncertain significance in 9 genes. Among the 28 variants of uncertain significance, 6 missense variants were found in highly conserved residues and were consistently predicted to be deleterious by in silico analyses. These results suggest that multigene panel testing is an effective approach for mutation screening in ALS-related genes. Moreover, the relatively low frequency of mutations in known ALS genes implies marked genetic heterogeneity at least in Korean patients with ALS.