Diagnostic Notch3 sequence analysis in CADASIL: three new mutations in Dutch patients. Dutch CADASIL Research Group.

To confirm the clinical diagnosis in individual Dutch patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), we performed direct sequence analysis of the abnormal gene, Notch3, in patients from 11 families without prior linkage analysis to chromosome 19. Eleven missense mutations involving the loss or gain of a cysteine residue were found, of which 3 are new. Exon 4 is a mutation hotspot (9 of 11 families). Notch3 sequence analysis of CADASIL patients in a diagnostic laboratory is a feasible procedure to confirm the clinical diagnosis in individual patients.