title: Extensive molecular genetic survey of Taiwanese patients with amyotrophic lateral sclerosis.
abstract: Identification of genetic mutations has been of burgeoning importance in amyotrophic lateral sclerosis (ALS) in recent years. The aim of this study was to determine the frequency and spectrum of mutations in major ALS-causing genes in a Taiwanese ALS cohort of Han Chinese origin. Mutational analyses of the SOD1, TARDBP, FUS, OPTN, VCP, UBQLN2, SQSTM1, PFN1, HNRNPA1, and HNRNPA2B1 genes were carried out by direct sequencing in 161 unrelated patients with ALS, including 30 with familial ALS (FALS) and 131 with sporadic ALS (SALS). The CAG repeat size in ATXN2 and the GGGGCC repeat expansion in C9ORF72 of the patients were also investigated. Mutations were identified in 33 patients (20.5%, 33/161), including 22 with FALS and 11 with SALS. Mutations were identified most frequently in SOD1 (7.5%). Three mutations are novel, including SOD1 p.G10A, SOD1 p.D83N, and OPTN p.L494W. These findings broaden the spectrum of ALS-causing mutations and are indispensable for designing optimal strategies of mutational analysis and genetic counseling of ALS for patients of Chinese origin.
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan; Brain Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Bing-Wen
authors.initials: BW
authors.lastname: Soong
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Kon-Ping
authors.initials: KP
authors.lastname: Lin
authors.affiliation: Department of Neurology, China Medical University Hospital, Taichung, Taiwan; School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Yuh-Cherng
authors.initials: YC
authors.lastname: Guo
authors.affiliation: Department of Neurology, National Cheng Kung University Hospital, Tainan, Taiwan; Department of Neurology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chou-Ching K
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan; Brain Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Pei-Chien
authors.initials: PC
authors.lastname: Tsai
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Yi-Chu
authors.initials: YC
authors.lastname: Liao
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Lu
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan; Brain Research Center, National Yang-Ming University, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Shuu-Jiun
authors.initials: SJ
authors.lastname: Wang
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan. Electronic address: cptsai@vghtpe.gov.tw.
authors.forename: Ching-Piao
authors.initials: CP
authors.lastname: Tsai
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan; Brain Research Center, National Yang-Ming University, Taipei, Taiwan. Electronic address: ycli@vghtpe.gov.tw.
authors.forename: Yi-Chung
authors.initials: YC
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D000067528:Ataxins; D000073885:C9orf72 Protein; D018797:Cell Cycle Proteins; D015331:Cohort Studies; D042622:DNA Repeat Expansion; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D011506:Proteins / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D013624:Taiwan / Q000453:epidemiology; D035582:Transcription Factor TFIIIA / Q000235:genetics; D055815:Young Adult
chemical_list: D000067528:Ataxins; D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C409460:OPTN protein, human; D011506:Proteins; C000606290:SOD1 protein, human; D035582:Transcription Factor TFIIIA; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: ALS; ATXN2; C9ORF72; FUS; HNRNPA1; OPTN; PFN1; SOD1; SQSTM1; TARDBP; UBQLN2; VCP