title: Identification of mutations in Korean patients with amyotrophic lateral sclerosis using multigene panel testing.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine, Green Cross Laboratories, Yongin-si, Gyeonggi-do, Korea.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Hanyang University College of Medicine, Seoul, Korea; Cell Therapy Center, Hanyang University Hospital, Seoul, Korea.
authors.forename: Ki-Wook
authors.initials: KW
authors.lastname: Oh
authors.affiliation: Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kwon
authors.affiliation: Department of Neurology, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.
authors.forename: Seong-Il
authors.initials: SI
authors.lastname: Oh
authors.affiliation: Department of Neurology, Hanyang University College of Medicine, Seoul, Korea; Cell Therapy Center, Hanyang University Hospital, Seoul, Korea.
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Kim
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Byung-Ok
authors.initials: BO
authors.lastname: Choi
authors.affiliation: Department of Brain and Cognitive Sciences, Seoul National University, Seoul, Korea.
authors.forename: Seungbok
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Electronic address: changski@skku.edu.
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.affiliation: Department of Neurology, Hanyang University College of Medicine, Seoul, Korea; Cell Therapy Center, Hanyang University Hospital, Seoul, Korea. Electronic address: kimsh1@hanyang.ac.kr.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D044466:Asian People; D005260:Female; D056726:Genetic Association Studies; D005820:Genetic Testing / Q000379:methods*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics*; D009154:Mutation; D000071456:Sequestosome-1 Protein; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D016875:tau Proteins / Q000235:genetics
chemical_list: C438187:ALS2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D020662:Guanine Nucleotide Exchange Factors; C054369:MAPT protein, human; C000606290:SOD1 protein, human; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D016875:tau Proteins; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: ALS; Amyotrophic lateral sclerosis; Multigene panel; Mutation; NGS; Next-generation sequencing