Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia (original) (raw)
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- Corpechot, Christophe ;
- Ducros, Anne ;
- Vahedi, Katayoun ;
- Chabriat, Hugues ;
- Mouton, Philippe ;
- Alamowitch, Sonia ;
- Domenga, Valérie ;
- Cécillion, Michaelle ;
- Maréchal, Emmanuelle ;
- Maciazek, Jacqueline ;
- Vayssière, Céline ;
- Cruaud, Corinne ;
- Cabanis, Emmanuel-Alain ;
- Ruchoux, Marie Madeleine ;
- Weissenbach, Jean ;
- Bach, Jean François ;
- Bousser, Marie Germaine ;
- Tournier-Lasserve, Elisabeth
Abstract
STROKE is the third leading cause of death, and vascular dementia the second cause of dementia after Alzheimer's disease. CADASIL (for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) causes a type of stroke and dementia whose key features include recurrent sub-cortical ischaemic events and vascular dementia and which is associated with diffuse white-matter abnormalities on neuro-imaging1,2. Pathological examination reveals multiple small, deep cerebral infarcts, a leukoencephalopathy, and a non-atherosclerotic, non-amyloid angiopathy involving mainly the small cerebral arteries3. Severe alterations of vascular smooth-muscle cells are evident on ultrastructural analysis4. We have previously mapped the mutant gene to chromosome 19 (ref. 5). Here we report the characterization of the human Notch3 gene which we mapped to the CADASIL critical region. We have identified mutations in CADASIL patients that cause serious disruption of this gene, indicating that Notch3 could be the defective protein in CADASIL patients.
Publication:
Nature
Pub Date:
October 1996
DOI:
Bibcode: