Identification of a Notch3 mutation in a Japanese CADASIL family

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leuk oencephalopathy (CADASIL) is a hereditary disease that is characterized by recurrent stroke episodes and focal neurologic deficits progressing to pseu dobulbar palsy and dementia. The causative gene is the Notch3 gene on chrom osome 19, and 22 missense mutations have been identified in Caucasian patie nts to date. To perform mutational analysis of the Notch3 gene, we identifi ed its exon-intron boundaries and prepared sets of primers for amplificatio n of each exon. Using these primers, we determined the Notch3 gene in a Jap anese family with CADASIL symptoms and found a missense mutation (Arg133Cys ) in exon 4. The mutation was heterozygous and cosegregated with the diseas e. Thus, the Notch3 gene is responsible for CADASIL in patients across diff erent ethnic groups.