title: [A novel mutation in glycyl-tRNA synthetase caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement].
abstract: BACKGROUND
  Charcot-Marie-Tooth disease (CMT) is a hereditary peripheral neuropathy; symptoms include distal wasting and weakness, usually with some sensory impairment. The clinical course is typically benign and the disease is not life threatening; however, in some cases, severe phenotypes include serious respiratory distress.
  
  
  METHODS
  Here we describe a 45-year-old woman with a long course of motor-dominant neuropathy. Distal weakness appeared in childhood and became worse with age. After a diagnosis of CMT type 2, the symptoms progressed, and in her fourth decade, facial and respiratory muscle weakness appeared, ultimately requiring non-invasive mechanical ventilation. There was no family history of CMT. Comprehensive analysis of known CMT-related genes revealed a novel heterozygous c.815T>A, p.L218Q mutation in glycyl-tRNA synthetase (GARS), a causative gene for both CMT type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V). This mutation was considered pathogenic based on molecular evidence; notably, it was unique in that all other reported GARS mutations associated with severe phenotypes are located in an anticodon-binding domain, while in this case in an apparently non-functional region of the GARS gene. Not a simple loss-of-function mechanism, but rather gain-of-function mechanisms have also been reported in GARS mutations. This case provided useful information for understanding the mechanism of CMT2D/dSMA-V.
authors.affiliation: Department of Neurology, Shizuoka General Hospital.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Kawakami
authors.forename: Kenichi
authors.initials: K
authors.lastname: Komatsu
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamashita
authors.forename: Kengo
authors.initials: K
authors.lastname: Uemura
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Oka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takashima
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
mesh_terms: D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology; D005152:Facial Muscles / Q000503:physiopathology*; D005260:Female; D006032:Glycine-tRNA Ligase / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D012132:Respiratory Muscles / Q000503:physiopathology*
chemical_list: D006032:Glycine-tRNA Ligase