Genetic study of familial vascular leukoencephalopathy

Research Project

Project/Area Number	09670685
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Neurology
Research Institution	National Center of Neurology and Psychiatry
Principal Investigator	TAKAHASHI Keikichi National Center of Neurology and Psychiatry, Institute of Neuroscience, Department of Demyelinating Disease and Aging, Division chief, 神経研究所, 室長 (40117148)
Project Period (FY)	1997 – 1998
Project Status	Completed (Fiscal Year 1998)
Budget Amount *help	¥3,200,000 (Direct Cost: ¥3,200,000) Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000) Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywords	Vascular leukoencephalopathy / Familial senile dementia / Notch3 gene / CADASIL / Signal transduction / Malti-infarct / Degeneration of brain artery / 老年期痴呆症 / 家族性痴呆症 / Notch3受容体 / Notchシグナル伝達系
Research Abstract	The Notch3 gene, located on chromosome l9p13.1, have been recently identified as a causative gene for Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). To investigate the genetic contribution of Notch mutations to familial vascular leukoencephalopathy, we screened 13 patients from 11 unrelated families with CADASIL-like symptoms and positive family history and identified three different missense mutations in five patients from 4 families. Two of which (Arg9Ocys and Argl33Cys) were the same as previously reported in Caucasian patients, the other (Cysl74Phe) was a novel mutation caused a loss of a cysteine in extracellular epidermal growth factor (EGF)-like repeats of Notch3. These data indicate that Notch3 gene is responsible for CADASIL patients in different ethnic groups, and its mutation frequency is approximately 35 % in familial leukoencephalopathy. However, there were also families in which no mutations in Notch3 were found, which indicates locus and /or allelic heterogeneity.