This variant was previously identified in a family affected by Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) [42], a rare hereditary cerebral small vessel disease associated with distinct low or incomplete penetrant NOTCH3 mutations and characterized by abnormalities in arterioles and capillaries, including abnormal pericyte–endothelial interactions, which compromise BBB integrity [66,67,68]. The gene discussed is NOTCH3; the disease is cerebral arteriopathy with subcortical infarcts and leukoencephalopathy.