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学科主题: 临床医学
题名:
Functional analysis of recently identified mutations in eukaryotic translation initiation factor 2B epsilon (eIF2B epsilon) identified in Chinese patients with vanishing white matter disease
作者: Leng, Xuerong2; Wu, Ye2; Wang, Xuemin1; Pan, Yanxia2,3; Wang, Jingmin2; Li, Jiao2,3; Du, Li2,3; Dai, Lifang2; Wu, Xiru2; Proud, Christopher G.1; Jiang, Yuwu2
关键词: Chinese ; childhood ataxia with central nervous system hypomyelination (CACH) ; eukaryotic translation initiation factor 2B (eIF2B) ; mutation ; vanishing white matter disease (VWM)
刊名: JOURNAL OF HUMAN GENETICS
发表日期: 2011-04-01
DOI: 10.1038/jhg.2011.9
卷: 56, 期:4, 页:300-305
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Genetics & Heredity
研究领域[WOS]: Genetics & Heredity
关键词[WOS]: FACTOR 2B COMPLEX ; PROTEIN-SYNTHESIS ; FACTOR EIF2B ; LEUKOENCEPHALOPATHY ; SUBUNIT ; LEUKODYSTROPHIES ; ACTIVATION ; SPECTRUM ; MUTANT ; GENES
英文摘要:

Vanishing white matter disease (VWM) is the first human hereditary disease known to be caused by defects in initiation of protein synthesis. Gene defects in each of the five subunits of eukaryotic translation initiation factor 2B (eIF2B alpha-beta) are responsible for the disease, although the mechanism of the pathogenesis is not well understood. In our previous study, four novel eIF2B epsilon mutat EP patients: p.Asp62Val, p.Cys335Ser, p.Asn376Asp and p.Ser610-Asp613del. Functional analysis was performed on these mutations and the recently reported p.Arg269X. Our data showed that all resulted in a decrease in the guanine nucleotide exchange (GEF) activity of the eIF2B complex. p.Arg269X and p. Ser610-Asp613del mutants displayed the lowest activity, followed by p.Cys335Ser, p.Asn376Asp and p.Asp62Val. p.Arg269X and p.Ser610-Asp613del could not produce stable eIF2B epsilon, leading to almost complete loss-of-function. No evidence was obtained for the three missense mutations in changes in eIF2B epsilon protein level or eIF2B epsilon Ser(540) phosphorylation, and disruption of holocomplex assembly, or binding to eIF2. All patients in our study had the classical phenotype. p.Asp62Val and p.Asn376Asp mutations caused only mildly decreased GEF activity, were probably responsible for relatively mild phenotype in cases of classical VWM. Journal of Human Genetics (2011) 56, 300-305; doi:10.1038/jhg.2011.9; published online 10 February 2011

语种: 英语
所属项目编号: 2006BAI05A07 ; 2007CB5119004 ; 30772355 ; 30872793 ; 7082093
项目资助者: National Key Research Project &prime ; 11-5&prime ; National Key Research Project &prime ; 973&prime ; Natural Science Foundation of China ; Natural Science Foundation of Beijing ; program for New Century Excellent Talents in University
WOS记录号: WOS:000289884500008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58002
Appears in Collections:北京大学第一临床医学院_儿科_期刊论文

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作者单位: 1.Shan Xi Med Univ, Dept Neurol, Taiyuan, Peoples R China
2.Univ Southampton, Div Human Genet, Southampton Gen Hosp, Southampton SO16 6YD, Hants, England
3.Peking Univ, Dept Pediat, Hosp 1, Beijing 100034, Peoples R China

Recommended Citation:
Leng, Xuerong,Wu, Ye,Wang, Xuemin,et al. Functional analysis of recently identified mutations in eukaryotic translation initiation factor 2B epsilon (eIF2B epsilon) identified in Chinese patients with vanishing white matter disease[J]. JOURNAL OF HUMAN GENETICS,2011,56(4):300-305.
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