Abstract
Of these inherited small vessel diseases, cerebral autosomal dominant arteriopathy with subcortical ischemic strokes and leukoencephalopathy (CADASIL) is the most frequent single-gene disorder caused by the mutations in the Notch3 gene located on chromosome 19p13. This Notch3 gene has 33 exons, but almost CADASIL mutations are clustered in exons 2–24. More than 95% of these mutations are missense mutations and most of which involve gain or loss of cysteine residue. However, despite the debates, novel mutation of R75P, not involving a cysteine residue, was reported in Asian populations, thus broadening the spectrum of CADASIL. The main symptoms include subcortical ischemic events, migraine, progressive cognitive decline, seizure, and psychiatric features. Typical diagnostic criteria of neuroimaging show severe white-matter hyperintensities usually involving anterior part of the temporal lobe and external capsules.
In contrast, previous studies suggested differences in the clinical and genetic spectrum of CADASIL between Asians and Caucasian populations. While exon 4 was the major Notch3 mutation sites in Caucasian population, exon 11 was the most common in Asian population. Although it is unclear that genetic differences might affect the phenotypes in ethnicities, Asian population shows less migraine or seizure, but more intracerebral hemorrhage. Furthermore, especially in patients with R75P mutations, the sensitivity of MRI detecting anterior temporal pole abnormalities was lower.
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Kim, Y. (2020). Cerebral Autosomal Dominant Arteriopathy with Subcortical Ischemic Strokes and Leukoencephalopathy (CADASIL). In: Lee, SH. (eds) Stroke Revisited: Pathophysiology of Stroke. Stroke Revisited. Springer, Singapore. https://doi.org/10.1007/978-981-10-1430-7_8
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