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Genetic study of familial vascular leukoencephalopathy

家族性血管性白质脑病的遗传学研究

基本信息

批准号：
09670685
负责人：
TAKAHASHI Keikichi
金额：
$ 2.05万
依托单位：
National Center of Neurology and Psychiatry
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670685/
关键词：
Vascular leukoencephalopathy Familial senile dementia Notch3 gene CADASIL Signal transduction Malti-infarct Degeneration of brain artery 老年期痴呆症家族性痴呆症 Notch3受容体 Notchシグナル伝達系

项目摘要

The Notch3 gene, located on chromosome l9p13.1, have been recently identified as a causative gene for Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). To investigate the genetic contribution of Notch mutations to familial vascular leukoencephalopathy, we screened 13 patients from 11 unrelated families with CADASIL-like symptoms and positive family history and identified three different missense mutations in five patients from 4 families. Two of which (Arg9Ocys and Argl33Cys) were the same as previously reported in Caucasian patients, the other (Cysl74Phe) was a novel mutation caused a loss of a cysteine in extracellular epidermal growth factor (EGF)-like repeats of Notch3. These data indicate that Notch3 gene is responsible for CADASIL patients in different ethnic groups, and its mutation frequency is approximately 35 % in familial leukoencephalopathy. However, there were also families in which no mutations in Notch3 were found, which indicates locus and /or allelic heterogeneity.

Notch3基因位于染色体19p13.1上，是近年来发现的常染色体显性遗传性脑动脉病皮质下梗塞和白质脑病的致病基因。为了探讨Notch基因突变在家族性血管白质脑病中的遗传作用，我们对11个家系中有CADASIL样症状和阳性家族史的13例患者进行了筛查，在4个家系中的5个患者中发现了3个不同的错义突变。其中两个(Arg9Ocys和Argl33Cys)与以前在高加索患者中报道的相同，另一个(Cysl74Phe)是一个新的突变，导致Notch3的细胞外表皮生长因子(EGF)样重复序列中的半胱氨酸丢失。这些数据表明Notch3基因与不同民族的CADASIL患者有关，其突变频率在家族性白质脑病中约为35%。然而，也有一些家系没有发现Notch3突变，这表明了基因和/或等位基因的异质性。