A novel AARS mutation in a family with dominant myeloneuropathy.
Neurology
; 84(20): 2040-7, 2015 May 19.
Article
em En
| MEDLINE
| ID: mdl-25904691
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Charcot-Marie-Tooth
/
Alanina-tRNA Ligase
/
Mutação
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article