The major hereditary IS diseases are cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy/arteriosclorosis with subcortical infarcts and leukoencephalopathy (CARASIL), and Fabry disease, which are caused by mutations in the notch receptor 3 (Notch3), htrA serine peptidase 1 (HTRA1), and galactosidase alpha (GLA) genes, respectively. The gene discussed is NOTCH3; the disease is cerebral arteriopathy with subcortical infarcts and leukoencephalopathy.