A novel AARS mutation in a family with dominant myeloneuropathy.
case_series · Level IV
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- Record sourced from PubMed, PMID 25904691.
- Also identified by DOI 10.1212/WNL.0000000000001583 and PMC identifier PMC3228828.
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Abstract
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.