title: Identification of a Notch3 mutation in a Japanese CADASIL family. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
abstract: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disease that is characterized by recurrent stroke episodes and focal neurologic deficits progressing to pseudobulbar palsy and dementia. The causative gene is the Notch3 gene on chromosome 19, and 22 missense mutations have been identified in Caucasian patients to date. To perform mutational analysis of the Notch3 gene, we identified its exon intron boundaries and prepared sets of primers for amplification of each exon. Using these primers, we determined the Notch3 gene in a Japanese family with CADASIL symptoms and found a missense mutation (Arg133Cys) in exon 4. The mutation was heterozygous and cosegregated with the disease. Thus, the Notch3 gene is responsible for CADASIL in patients across different ethnic groups.
authors.affiliation: Department of Demyelinating Disease and Aging, National Institute of Neuroscience, National Center for Neurology and Psychiatry, Kodaira, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kamimura
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: E
authors.initials: E
authors.lastname: Uyama
authors.forename: M
authors.initials: M
authors.lastname: Tokunaga
authors.forename: S
authors.initials: S
authors.lastname: Kotorii
authors.forename: M
authors.initials: M
authors.lastname: Uchino
authors.forename: T
authors.initials: T
authors.lastname: Tabira
mesh_terms: D015161:Dementia, Multi-Infarct / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D051880:Receptors, Notch
chemical_list: D008565:Membrane Proteins; D051880:Receptors, Notch