title: The G526R glycyl-tRNA synthetase gene mutation in distal hereditary motor neuropathy type V.
abstract: BACKGROUND
  Distal hereditary motor neuropathy (dHMN) or distal spinal muscular atrophy (dSMA) is a heterogeneous group of disorders characterized almost exclusively by degeneration of motor nerve fibers, predominantly in the distal part of the limbs. One subtype, dHMN type V (dHMN-V), is transmitted by autosomal dominant inheritance and predominantly involves the hands. It is allelic with Charcot-Marie-Tooth disease 2D (CMT2D), in which a similar phenotype is associated with sensory signs. Missense mutations in the glycyl-tRNA synthetase (GARS) gene have been recently reported in families with either dHMN-V, CMT2D, or both.
  
  
  METHODS
  The authors searched for GARS mutations in eight dHMN-V families.
  
  
  RESULTS
  The authors found the G526R missense mutation in three families (16 patients) of Algerian Sephardic Jewish origin. All patients shared a common disease haplotype, suggestive of a founder effect. The clinical phenotype consists of a slowly progressive, purely motor distal neuropathy. It starts in the hands in most patients, but also in both distal upper and lower limbs or in distal lower limbs alone. The age at onset in symptomatic individuals was between the second to fourth decades, but four mutation carriers were still asymptomatic, two of whom were already age 49 years. Electrophysiology showed that the motor fibers of the median nerve were the most affected in upper limbs. Sensory nerve action potentials were normal.
  
  
  CONCLUSIONS
  The age at onset of patients with the G526R mutation in the GARS gene varied widely, but the clinical and electrophysiologic presentation was uniform and progressed slowly. Glycyl-tRNA synthetase mutations are a frequent cause of familial distal hereditary motor neuropathy type V but, because of the reduced penetrance of the disease, could also account for isolated cases.
authors.affiliation: INSERM U679, Consultation Pluridisciplinaire des Neuropathies Héréditaires, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. dubourg@ccr.jussieu.fr
authors.forename: O
authors.initials: O
authors.lastname: Dubourg
authors.forename: H
authors.initials: H
authors.lastname: Azzedine
authors.forename: R Ben
authors.initials: RB
authors.lastname: Yaou
authors.forename: J
authors.initials: J
authors.lastname: Pouget
authors.forename: A
authors.initials: A
authors.lastname: Barois
authors.forename: V
authors.initials: V
authors.lastname: Meininger
authors.forename: D
authors.initials: D
authors.lastname: Bouteiller
authors.forename: M
authors.initials: M
authors.lastname: Ruberg
authors.forename: A
authors.initials: A
authors.lastname: Brice
authors.forename: E
authors.initials: E
authors.lastname: LeGuern
mesh_terms: D017668:Age of Onset; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006032:Glycine-tRNA Ligase / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D007585:Jews / Q000235:genetics; D009134:Muscular Atrophy, Spinal / Q000453:epidemiology* / Q000235:genetics*; D009154:Mutation; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors
chemical_list: D006032:Glycine-tRNA Ligase