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.

• PMID: 25904691
• DOI full text
• PMC full text
• PubMed

Reference Type

Journal Article | Research Support, N.I.H., Extramural

Authors

Motley WW, Griffin LB, Mademan I, Baets J, De Vriendt E, De Jonghe P, Antonellis A, Jordanova A, Scherer SS

Primary Lit For

Additional Lit For

Review For