identification of a known mutation in notch 3 in familiar cadasil in china识别已知的突变在切口3熟悉cadasil在中国.pdfVIP

Identification of a Known Mutation in Notch 3 in Familiar CADASIL in China 1. 1 . 2. 1. 1 3 2 Zhen-Xuan Tan , Fei-Feng Li * , You-Yang Qu , Ji Liu , Gui-Rong Liu , Jin Zhou , Yu-Lan Zhu *, Shu- Lin Liu1,3,4* 1 Genomics Research Center, Harbin Medical University, Harbin, China, 2 Neurology Department of The Second Affiliated Hospital, Harbin Medical University, Harbin, China, 3 Genetic Detection Center of The First Clinical College, Harbin Medical University, Harbin, China, 4 Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Canada Abstract Background: 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 and Results: We 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. Conclusions: Members of a 5-generational Han Chinese family with CADASIL patients had an R133C mutation in the NOTCH3 gene but only individuals exposed to know