CADASIL.
CADASIL.
复制标题
DOI：
10.1016/b978-0-444-64076-5.00047-8
复制
发表时间：
2018-01-01
影响因子：
--
通讯作者：
Wang, Michael M
中科院分区：
文献类型：
--
作者：
Wang, Michael M
脑小血管疾病是一种与缺血性中风和痴呆密切相关的常见疾病。脑小血管疾病最常见的遗传原因是CADASIL，即伴有皮质下梗死和白质脑病的常染色体显性脑动脉病，这是一种与NOTCH 3突变相关的疾病。CADASIL最常见的症状是小的缺血性中风和/或短暂性脑缺血发作和认知障碍，出现在中年，可能进展为坦率的血管性痴呆。然而，人们越来越认识到，个体症状类型，发病和疾病严重程度跨越广泛的范围，甚至在同一家庭的个体之间。CADASIL的磁共振成像显示严重的白质高信号，既往皮质下卒中的证据，以及在某些情况下的微血管病变。在CADASIL中，已经在全世界描述了NOTCH 3中的数百个突变，并且几乎所有这些突变都改变了细胞外NOTCH 3基因产物的半胱氨酸含量。CADASIL的这种分子遗传特征导致了血管平滑肌蛋白NOTCH 3的结构异常引发动脉变性、血管蛋白积聚和脑血管衰竭的假设。
Cerebral small-vessel disease is a prevalent condition that is strongly associated with ischemic stroke and dementia. The most prevalent inherited cause of cerebral small-vessel disease is CADASIL, cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, a disorder linked to mutations in NOTCH3. The most common symptoms of CADASIL are small ischemic strokes and/or transient ischemic attacks and cognitive impairment, appearing in middle age, that may progress to frank vascular dementia. However, it is increasingly recognized that individual symptom types, onset, and disease severity span a wide spectrum, even among individuals in the same family. Magnetic resonance imaging in CADASIL reveals severe white-matter hyperintensities, evidence of prior subcortical strokes, and, in some cases, microhemorrhages. Several hundred mutations in NOTCH3 have been described worldwide in CADASIL, and virtually all of these mutations alter the cysteine content of the extracellular NOTCH3 gene product. This molecular genetic signature of CADASIL has led to the hypothesis that structural abnormalities in the vascular smooth-muscle protein NOTCH3 trigger arterial degeneration, vascular protein accumulation, and cerebrovascular failure.