Spectrum of mutations in biopsy-proven CADASIL: implications for diagnostic strategies

Background: Mutations in the NOTCH3 gene are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is an important cause of stroke in young adults. Mutations are typically located within epidermal growth factor (EGF) -like repeat domains in the extracellular part of the Notch3 receptor. Identification of the mutation is critical for genetic counseling and testing of relatives at risk. Objective: To identify the spectrum of NOTCH3 mutations in CADASIL and to discuss the implications for diagnostic strategies. Design: Screening for NOTCH3 mutations…