Cerebral autosomal dominant arteriopathy. with subcortical infarcts and leu
koencephalopathy (CADASIL) is an adult-onset disorder presenting as vascula
r dementia associated with mutations of Notch3 gene. To clarify the occurre
nce of CADASIL in Orientals, we performed clinicogenetic studies for 5 unre
lated Japanese families presenting as CADASIL. On mutational analysis of No
tch3 gene, we identified R133C mutation in two unrelated families including
5 affected individuals. Their clinicopathological findings shared similar
patterns as European CADASIL families. Other 3 unrelated families including
18 affected individuals presenting with CADASIL-like clinical features dis
closed no mutations of Notch3 gene. Thus, the results indicate that CADASIL
is a geographically widespread disorder, and there are unknown hereditary
arteriopathies resulting in vascular dementia without Notch3 mutations in J
apan.