Diagnostic Notch3 sequence analysis in CADASIL: Three new mutations in Dutch patients

To confirm the clinical diagnosis in individual Dutch patients with cerebra l autosomal dominant arteriopathy with subcortical infarcts and leukoenceph alopathy (CADASIL), we performed direct sequence analysis of the abnormal g ene, Notch3, in patients from 11 families without prior linkage analysis to chromosome 19. Eleven missense mutations involving the loss or gain of a c ysteine residue were found, of which 3 are new. Exon 4 is a mutation hotspo t (9 of 11 families). Notch3 sequence analysis of CADASIL patients in a dia gnostic laboratory is a feasible procedure to confirm the clinical diagnosi s in individual patients.