title: Two Novel De Novo GARS Mutations Cause Early-Onset Axonal Charcot-Marie-Tooth Disease.
abstract: BACKGROUND
  Mutations in the GARS gene have been identified in a small number of patients with Charcot-Marie-Tooth disease (CMT) type 2D or distal spinal muscular atrophy type V, for whom disease onset typically occurs during adolescence or young adulthood, initially manifesting as weakness and atrophy of the hand muscles. The role of GARS mutations in patients with inherited neuropathies in Taiwan remains elusive.
  
  
  RESULTS
  Mutational analyses of the coding regions of GARS were performed using targeted sequencing of 54 patients with molecularly unassigned axonal CMT, who were selected from 340 unrelated CMT patients. Two heterozygous mutations in GARS, p.Asp146Tyr and p.Met238Arg, were identified; one in each patient. Both are novel de novo mutations. The p.Asp146Tyr mutation is associated with a severe infantile-onset neuropathy and the p.Met238Arg mutation results in childhood-onset disability.
  
  
  CONCLUSIONS
  GARS mutations are an uncommon cause of CMT in Taiwan. The p.Asp146Tyr and p.Met238Arg mutations are associated with early-onset axonal CMT. These findings broaden the mutational spectrum of GARS and also highlight the importance of considering GARS mutations as a disease cause in patients with early-onset neuropathies.
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; Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Yo-Tsen
authors.initials: YT
authors.lastname: Liu
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: Pei-Chien
authors.initials: PC
authors.lastname: Tsai
authors.affiliation: Institute of BioMedical Informatics, National Yang-Ming University School of Medicine, Taipei, Taiwan; Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chia-Ching
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Institute of BioMedical Informatics, National Yang-Ming University School of Medicine, Taipei, Taiwan; Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yen-Hua
authors.initials: YH
authors.lastname: Huang
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; Brain Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yi-Chung
authors.initials: YC
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D001483:Base Sequence; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D006032:Glycine-tRNA Ligase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult
chemical_list: D006032:Glycine-tRNA Ligase