Novel GARS mutation presenting as autosomal dominant intermediate Charcot-Marie-Tooth disease

J Peripher Nerv Syst. 2019 Mar;24(1):156-160. doi: 10.1111/jns.12289. Epub 2018 Nov 23.

Abstract

We report the first family with a glycyl-tRNA synthetase (GARS) mutation with autosomal dominant intermediate Charcot-Marie-Tooth disease (DI-CMT). The proband and the proband's father presented with gait disturbance and hand weakness. Both patients displayed moderately decreased conduction velocities (MNCV) (ranging from 29.2 to 37.8 m/s). A sural nerve biopsy of the father revealed evidence of both axonal loss and demyelination. On exome sequencing, in both the proband and his father, we identified a novel missense mutation (c.643G > C, p.Asp215His) in the GARS gene in a heterozygous state, which is considered to be pathogenic for this DI-CMT family. The present study broadens current knowledge about intermediate CMT and the phenotypic spectrum of defects associated with GARS.

Keywords: ARSs; GARS; autosomal dominant intermediate CMT; missense mutation; nerve biopsy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Charcot-Marie-Tooth Disease / genetics*
  • Charcot-Marie-Tooth Disease / pathology
  • Charcot-Marie-Tooth Disease / physiopathology
  • Glycine-tRNA Ligase / genetics*
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense
  • Neural Conduction / physiology
  • Pedigree
  • Sural Nerve / pathology
  • Young Adult

Substances

  • Glycine-tRNA Ligase