NOTCH3 mutation involving three cysteine residues in a family with typicalCADASIL

Mutations in NOTCH3 are the cause of cerebral autosomal dominant arteriopat hy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditar y angiopathy causing stroke and vascular dementia. All CADASIL mutations id entified so far result in the loss or gain of one cysteine residue within e pidermal growth factor (EGF)-like repeat domains. Here an in-frame deletion causing a loss of three cysteine residues within EGF repeat 6 is reported. These data are consistent with the hypothesis that the change toward an od d number of cysteine residues within a given EGF repeat and therefore an un paired, reactive cysteine residue is the common and critical molecular even t in CADASIL.