NEXT GENERATION SEQUENCING AND EXPERIMENTAL MYOLOGY: P.375Application of next-generation sequencing using customized targeted gene panel for neuromuscular disorders in South Korea

Abstract

Next generation sequencing (NGS) has been currently known for efficient diagnostic method for diagnosing genetic disorders, including neuromuscular disorders. But, we could have a difficulty in diagnosing neuromuscular disorders, which have clinical and genetic heterogeneity. With this study, we aimed to evaluate the diagnostic yield of current targeted NGS using our customized gene panel. We developed targeted gene panels including 172 candidate genes for neuropathy panel and 213 candidate genes for muscular disorder panel. We performed NGS using customized gene panel for 102 patients with neuromuscular disorder from January 1, 2017 to February 28, 2018. According to clinical manifestation, there are several patient groups, including motor neuron disease (n=22), hereditary neuropathy (n=12), hereditary spastic paraplegia (n=10), inherited muscular disorder (n=26), idiopathic hyperCKemia (n=4), channelopathy (n=7), and the rest of patients. We identified 22 patients (22.5%) with genetic confirmation using targeted NGS. 19 patients had pathogenic or likely pathogenic SNVs in 14 genes, including SPAST (n=3), DYSF (n=3), TTN (n=2), DMD, GNE, SCN4A, FUS, KIF5A, MUSK, DNAJB6, MYH3, CACNA1S, GJB1, ABCD1 (n=1). 3 patients had pathogenic or likely pathogenic CNVs (1 duplication and 1 deletion of PMP, exon 9-16 duplication of SPAST). After NGS testing, the other 2 patients were diagnosed as myotonic muscular dystrophy type 1 with increased CTG repeat of DMPK, and spinal and bulbar muscular atrophy with increased CAG repeat of AR, respectively. NGS using customized gene panel is useful for diagnosis of neuromuscular disorder when we diagnosed the specific disease. We can increase the efficacy of NGS with specific criteria for NGS and standardization of diagnostic approach.