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 known vascular risk factors developed CADASIL.