Identification of novel EIF2B mutations in Chinese patients with vanishing white matter disease
Identification of novel EIF2B mutations in Chinese patients with vanishing white matter disease
复制标题
中国白质消失病患者中新型 EIF2B 突变的鉴定
DOI：
10.1038/jhg.2008.10
复制
发表时间：
2009-02-01
影响因子：
3.5
通讯作者：
Jiang, Yuwu
中科院分区：
文献类型：
--
作者：
Wu, Ye;Pan, Yanxia;Jiang, Yuwu
消失性白色物质（VWM）病，以常染色体隐性方式遗传，是儿童期最常见的遗传性白质脑病之一。它是一种由蛋白质合成过程中的直接缺陷引起的人类遗传性疾病，EIF 2B 1 -5（2001-2002年鉴定）中的基因缺陷分别编码真核翻译起始因子的五个亚基（eIF 2B alpha、beta、gamma、delta和epsilon）。大多数已发表的研究是在白色人群中进行的。首次对11例中国患者进行临床特征分析和EIF 2B突变筛查。在这些患者中，仅在EIF 2B 5和EIF 2B 3中发现了突变，其中有6个新突变，包括5个错义突变（EIF 2B 5：c.185A>T，p.D62V; c.1004G>C，p.C335S; c.1126A>G，p.N376D; EIF 2B 3：c.140G>A，p.G47E; c.1037T>C，p.I346T）和一个导致氨基酸缺失的缺失（EIF2B5：c.1827-1838del，p.S610-D613del）。EIF 2B 3突变占本研究中发现的突变总数的20%，比早期报告（7%）预期的更普遍。在这项研究中发现了EIF 2B 3的热点突变。中国VWM患者存在独特的EIF 2B突变谱。需要进行系统的研究，以评估不同人群的突变谱。
Vanishing white matter (VWM) disease, inherited in an autosomal recessive manner, is one of the most prevalent inherited leukoencephalopathies in childhood. It is a hereditary human disease resulting from the direct defects during protein synthesis, with the gene defects in EIF2B1-5 (identified in 2001-2002) encoding the five subunits of eukaryotic translation initiation factor (eIF2B alpha, beta, gamma, delta and epsilon), respectively. Most of the published studies were carried out in the white population. The analysis of clinical features and EIF2B mutation screening were performed in 11 Chinese patients for the first time. Mutations were identified exclusively in EIF2B5 and EIF2B3 in these patients, with six novel mutations, including five missense mutations (EIF2B5: c.185A>T, p.D62V; c.1004G>C, p.C335S; c.1126A>G, p.N376D; EIF2B3: c.140G>A, p.G47E; c.1037T>C, p.I346T) and one deletion leading to amino-acid deletion (EIF2B5: c.1827-1838del, p.S610-D613del). EIF2B3 mutation, accounting for 20% of the total number of mutations found in this study, is more prevalent than expected according to an earlier report (7%). A hot spot mutation in EIF2B3 was identified in this study. A unique EIF2B mutation spectrum in Chinese VWM patients was shown. A systemic study to assess mutation spectrum in different populations needs to be carried out.