Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia
Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia
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DOI：
10.1038/383707a0
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发表时间：
1996-10-24
期刊：
影响因子：
64.8
通讯作者：
TournierLasserve, E
中科院分区：
文献类型：
--
作者：
Joutel, A;Corpechot, C;TournierLasserve, E
中风是第三大死亡原因，血管性痴呆是继阿尔茨海默氏病之后的第二大痴呆原因。CADASIL（常染色体显性遗传性脑动脉病伴皮质下梗死和白质脑病）可导致一种中风和痴呆，其主要特征包括复发性皮质下缺血事件和血管性痴呆，并与神经影像学上的弥漫性白质异常相关（1，2）。病理学检查显示多发性小的深部脑梗死、白质脑病和非动脉粥样硬化性、非淀粉样血管病，主要累及小脑动脉（3）。血管平滑肌细胞的严重改变在超微结构分析中是明显的（4）。我们先前已将突变基因定位于19号染色体（参考文献5）。在这里，我们报告的人Notch3基因，我们映射到CADASIL关键区域的表征。我们已经在CADASIL患者中发现了导致该基因严重破坏的突变，表明Notch3可能是CADASIL患者中的缺陷蛋白。
STROKE is the third leading cause of death, and vascular dementia the second cause of dementia after Alzheimer's disease. CADASIL (for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) causes a type of stroke and dementia whose key features include recurrent subcortical ischaemic events and vascular dementia and which is associated with diffuse white-matter abnormalities on neuroimaging(1,2). Pathological examination reveals multiple small, deep cerebral infarcts, a leukoencephalopathy, and a non-atherosclerotic, non-amyloid angiopathy involving mainly the small cerebral arteries(3). Severe alterations of vascular smooth-muscle cells are evident on ultrastructural analysis(4). We have previously mapped the mutant gene to chromosome 19 (ref. 5). Here we report the characterization of the human Notch3 gene which we mapped to the CADASIL critical region. We have identified mutations in CADASIL patients that cause serious disruption of this gene, indicating that Notch3 could be the defective protein in CADASIL patients.