A novel AARS mutation in a family with dominant myeloneuropathy
A novel AARS mutation in a family with dominant myeloneuropathy
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DOI：
10.1212/wnl.0000000000001583
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发表时间：
2015-05-19
期刊：
影响因子：
9.9
通讯作者：
Scherer, Steven S.
中科院分区：
文献类型：
--
作者：
Motley, William W.;Griffin, Laurie B.;Scherer, Steven S.
目的：目的：探讨一个脊髓神经病家系神经退行性变的遗传原因。方法：我们对一个轻度显性遗传性神经病家系的5名同胞进行了临床检查和电生理检查。1例患者行腓肠神经活检。排除常见的遗传原因轴突Charcot-Marie-Tooth病后，我们测序3 tRNA合成酶基因与neuropathy.Results：所有受影响的家庭成员有轻度轴突神经病变，3 4下肢反射亢进，叠加脊髓病的证据。神经活检显示慢性轴突丢失的证据。所有受影响的家族成员都在丙氨酰-tRNA合成酶（阿尔斯）基因中存在杂合错义突变c.304 G>C（p.Gly102 Arg）;在未受影响的个体或对照样本中未发现该等位基因。在酵母直系同源物中的等效变化未能补充缺乏阿尔斯功能的酵母菌株，这表明突变是damage.Conclusion：一种新的突变在阿尔斯导致轻度的脊髓神经病，一种新的表型的tRNA合成酶基因突变的患者。
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.