Mutations in the NOTCH3 gene are responsible for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), adult-onset hereditary angiopathy leading to ischemic episodes, vascular dementia, and other neurologic deficits. Here, NOTCH3 is linked to cerebral arteriopathy with subcortical infarcts and leukoencephalopathy.