NOTCH3 mutations in a cohort of Portuguese patients within CADASIL spectrum phenotype.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common inherited cerebral small vessel disease. It is caused by mutations in the NOTCH3 gene, which encodes a membranebound receptor protein with three main distinct functional domains. Thus far, several different NOTCH3 mutations, most of them cysteine altering variants, have been described and although they tend to cluster in certain exons, their distribution varies in different geographically populations.

SQSTM1 gene as a potential genetic modifier of CADASIL phenotype.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common inherited cerebral small vessel disease and is caused by mutations in the NOTCH3 gene. Interestingly, CADASIL patients present a large phenotypic variability even harboring the same pathogenic variant. We describe two CADASIL siblings with a particularly aggressive clinical phenotype characterized by early-onset stroke, gait disturbances and/or dementia, severe emotional dysregulation, and dysexecutive syndrome together with a severe white matter burden on MRI.