A novel mutation in glycyl-tRNA synthetase caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement

Nobuko Kawakami, Kenichi Komatsu, Hirofumi Yamashita, Kengo Uemura, Nobuyuki Oka, Hiroshi Takashima, Ryosuke Takahashi

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

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. CASE REPORT: 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)f 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 nonfunctional 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.

Original languageEnglish
Pages (from-to)911-915
Number of pages5
JournalClinical Neurology
Volume54
Issue number11
DOIs
Publication statusPublished - 2014

Keywords

  • Charcot-Marie-Tooth disease
  • Glycine-tRNA ligase
  • Hereditary sensory and motor neuropathy
  • Respiratory distress
  • Spinal muscular atrophy

ASJC Scopus subject areas

  • Clinical Neurology

Fingerprint Dive into the research topics of 'A novel mutation in glycyl-tRNA synthetase caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement'. Together they form a unique fingerprint.

Cite this