A novel AARS mutation in a family with dominant myeloneuropathy

Neurology. 2015 May 19;84(20):2040-7. doi: 10.1212/WNL.0000000000001583. Epub 2015 Apr 22.


Objective: To determine the genetic cause of neurodegeneration in a family with myeloneuropathy.

Methods: We studied 5 siblings in a family with a mild, dominantly inherited neuropathy by clinical examination and electrophysiology. One patient had a sural nerve biopsy. After ruling out common genetic causes of axonal Charcot-Marie-Tooth disease, we sequenced 3 tRNA synthetase genes associated with neuropathy.

Results: All affected family members had a mild axonal neuropathy, and 3 of 4 had lower extremity hyperreflexia, evidence of a superimposed myelopathy. A nerve biopsy showed evidence of chronic axonal loss. All affected family members had a heterozygous missense mutation c.304G>C (p.Gly102Arg) in the alanyl-tRNA synthetase (AARS) gene; this allele was not identified in unaffected individuals or control samples. The equivalent change in the yeast ortholog failed to complement a strain of yeast lacking AARS function, suggesting that the mutation is damaging.

Conclusion: A novel mutation in AARS causes a mild myeloneuropathy, a novel phenotype for patients with mutations in one of the tRNA synthetase genes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alanine-tRNA Ligase / genetics*
  • Axons / ultrastructure
  • Charcot-Marie-Tooth Disease / genetics*
  • Family
  • Female
  • Genes, Dominant
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree
  • Sural Nerve / ultrastructure
  • Young Adult


  • Alanine-tRNA Ligase