The spectrum of Notch3 mutations in 28 Italian CADASIL families.

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a cause of hereditary cerebrovascular disease. It results from mutations in the Notch3 gene, a large gene with 33 exons. A cluster of mutations around exons 3 and 4 was originally reported and limited scanning of these exons was suggested for the diagnosis in most cases. To report Notch3 mutation analysis in 28 unrelated Italian CADASIL families from central and south Italy. The highest rate of mutations was found in exon 11 (21%) and only 18% of mutations were in exon 4. This may be related to the peculiar distribution of Notch3 mutations in the regions of origin of the families. The results suggest that limited scanning of exons 3 and 4 is inadvisable in CADASIL cases of Italian origin.