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Title
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A novel AARS mutation in a family with dominant myeloneuropathy
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Neurology / American Academy of Neurology. - Minneapolis, Minn
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Publication
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Minneapolis, Minn
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2015
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ISSN
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0028-3878
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DOI
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10.1212/WNL.0000000000001583
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Volume/pages
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84
:20
(2015)
, p. 2040-2047
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ISI
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000369760100010
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Pubmed ID
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25904691
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Full text (Publisher's DOI)
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Full text (open access)
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