Mutational spectrum and clinical features in 35 unrelated mainland Chinese patients with GNE myopathy
Mutational spectrum and clinical features in 35 unrelated mainland Chinese patients with GNE myopathy
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35例中国大陆无亲属关系的GNE肌病患者的突变谱和临床特征
DOI：
10.1016/j.jns.2015.04.028
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发表时间：
2015-07-15
影响因子：
4.4
通讯作者：
Yuan, Yun
中科院分区：
文献类型：
--
作者：
Zhao, Juan;Wang, Zhaoxia;Yuan, Yun
GNE 肌病是一种由 GNE 基因双等位基因突变引起的常染色体隐性远端肌病。不同种族之间表现出巨大的遗传异质性。在这项研究中，我们总结了来自中国大陆的 35 名无关 GNE 肌病患者的突变谱和临床特征。分子分析揭示了 16 个新蛋白（p.G47D、p.F66Y、p.E173A、p.Y186H、p.R246L、p.R263*、p.R306*、p.A366D、p.V512M、p.C520Y、p.G545R、p.G548S、p.V622G、 p.A638P，IVS2 + 1G > A 和 c2112delC) 和 13 个报告的突变。值得注意的是，该患者队列中 65.7% (23/35) 的患者检测到 p.D176V 突变，等位基因频率为 34.3% (24/70)。我们估计正常人群中 p.D176V 的携带频率为 0.19% (1/520)，尽管单倍型分析表明携带 p.D176V 突变的患者没有创始人效应。临床上，29 名患者呈现以远端无力为主的经典表型，而 6 名患者则呈现非典型表型。然而，肌肉磁共振成像显示，两个亚组的股外侧肌均未受影响。总之，GNE 基因中的 p.D176V 突变是日本患者中第二常见的突变，也是该中国患者队列中最常见的突变。本研究中发现的新 GNE 突变扩大了与 GNE 肌病相关的突变谱。 GNE 肌病患者之间存在表型异质性，但肌肉磁共振成像可用于鉴别诊断。 (C) 2015 Elsevier B.V. 保留所有权利。
GNE myopathy is an autosomal recessive distal myopathy caused by biallelic mutation in the GNE gene. It shows great genetic heterogeneity among different ethnic groups. In this study, we summarized the mutational spectrum and clinical profiles in 35 unrelated GNE myopathy patients from mainland China. Molecular analysis revealed 16 novel (p.G47D, p.F66Y, p.E173A, p.Y186H, p.R246L, p.R263*, p.R306*, p.A366D, p.V512M, p.C520Y, p.G545R, p.G548S, p.V622G, p.A638P, IVS2 + 1G > A and c2112delC) and 13 reported mutations. Notably, the p.D176V mutation was detected in 65.7% (23/35) of this patient cohort, giving an allele frequency of 34.3% (24/70). We estimated the carrier frequency of p.D176V to be 0.19% (1/520) in the normal population, although haplotype analysis indicated no founder effect in the patients carrying p.D176V mutation. Clinically, 29 patients presented with the classic phenotype of predominant distal weakness, while six patients presented with atypical phenotype. However, muscle magnetic resonance imaging showed that the vastus lateralis was spared in both subgroups. In conclusion, p.D176V mutation in the GNE gene, which was the second most common mutation in Japanese patients, was the most common mutation in this cohort of Chinese patients. Novel GNE mutations found in this study expanded the mutational spectrum associated with GNE myopathy. There is phenotypic heterogeneity among patients with GNE myopathy, but muscle magnetic resonance imaging can be useful for differential diagnosis. (C) 2015 Elsevier B.V. All rights reserved.