1998 Fiscal Year Final Research Report Summary
Genetic study of familial vascular leukoencephalopathy
| Project/Area Number |
09670685
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | National Center of Neurology and Psychiatry |
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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)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Vascular leukoencephalopathy / Familial senile dementia / Notch3 gene / CADASIL / Signal transduction / Malti-infarct / Degeneration of brain artery |
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| 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.
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