Identification of a Known Mutation in Notch 3 in Familiar CADASIL in China

Zhen-Xuan Tan,Yu-Lan Zhu,Ji Liu,Shu-Lin Liu,Jin Zhou,Fei-Feng Li,You-Yang Qu,Gui-Rong Liu,David R Borchelt

doi:10.1371/journal.pone.0036590

Abstract

BackgroundCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease leading to recurrent ischemic stroke and vascular dementia. Numerous mutations in the 23 exons of the NOTCH3 gene have been reported to cause CADASIL in Caucasian populations, but the full spectrum of genetic changes leading to this disease is yet to be known and, especially, very few reports are available on CADASIL in Asian populations.Methods and ResultsWe genotyped members of a 5-generational Han Chinese family with CADASIL patients and identified an R133C mutation in the NOTCH3 gene. Clinical analysis demonstrated that the penetrance of the mutation was not complete. Five of the mutation carriers, not exposed to the known vascular risk factors, did not show any clinical feature of CADASIL, suggesting the importance of environmental factors to the development of this disease.ConclusionsMembers of a 5-generational Han Chinese family with CADASIL patients had an R133C mutation in the NOTCH3 gene but only individuals exposed to known vascular risk factors developed CADASIL.

Highlights

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease with mutations in the NOTCH3 gene [1,2,3]
Members of a 5-generational Han Chinese family with CADASIL patients had an R133C mutation in the NOTCH3 gene but only individuals exposed to known vascular risk factors developed CADASIL
The main clinical feature of the disease is the disfunctioning of the central nervous system (CNS), characterized by recurrent ischemic attacks or strokes, migraine, cognitive impairment, dementia and psychiatric disturbances [7]

Summary

Introduction

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease with mutations in the NOTCH3 gene [1,2,3]. This disorder has been found in many race-ethnicities, with most reported cases coming from European Caucasian families [2,4,5]. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease leading to recurrent ischemic stroke and vascular dementia. Numerous mutations in the 23 exons of the NOTCH3 gene have been reported to cause CADASIL in Caucasian populations, but the full spectrum of genetic changes leading to this disease is yet to be known and, especially, very few reports are available on CADASIL in Asian populations

Methods

Results

Conclusion