First Mexican Family with CADASIL: A Novel Mutation in the NOTCH3 Gene (P07.242)

OBJECTIVE: Describe the clinical, imaging and genetic features of the first Mexican family with CADASIL. BACKGROUND: Mutations in the NOTCH3 gene are responsable of (CADASIL, an adult onset hereditary angiopathy leading to ischemic stroke, vascular dementia and psychiatric disorders. All mutation of NOTCH3 described so far are striking stereotyped leading to the gain or loss of cystiene residue in a given epidermal growth factor (EGF). DESIGN/METHODS: Three members of a single Mexican family from the state of Sinaloa (North-East region of Mexico) were genetically studied in search of CADASIL confirmation. The patients come from four generations family in which there were at least 18 members with clinical data suggestive of of CADASIL (Migraine, Depression; Strokes, Dementia). DNA was extracted from whole blood using standard procedures. RESULTS: The family is a native Mexican family settled in Sinaloa, Northwestern part of the country. The proband is a female seen at age 48 years with history of migraine. An brain MRI disclosed whitte matter and periventricular abnormalities as well FLAIR and T2 hyperintensities in temporal anterior poles and basal ganglia. Her father died at age 63 years after 6 years of history with repeated strokes and dementia. Two patternal uncles with history of multiple strokes and dementia. She has fourteen siblings, six of them with history of depression, multiple stroke and dementia. Five of them are alive and with abnormalities in brain MRI.One nephew with migraine and a brother with clinical spectrum of CADASIL were eavluated in search of notch3 mutation. We identified a heterozygous point mutation in exon 3 of NOTCH 3 (c.304T>A). This mutation was detected in all 3 patients. This is a mutation typical of CADASIL. CONCLUSIONS: Clinical, imaging and genetic characterisitics of the first mexican family with CADASIL are presented. The clinical findings are similar to those presented in other races with CADASIL. Disclosure: Dr. Barinagarrementeria has nothing to disclose. Dr. Arauz has nothing to disclose. Dr. Mine has nothing to disclose.