Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) associated with a Novel C82R Mutation in the NOTCH3 Gene

Article type: Short Communication

Authors: Zea-Sevilla, Mª Ascensión^{a; *} | Bermejo-Velasco, Pedro^b | Serrano-Heranz, Regino^c | Calero, Miguel^{a; d}

Affiliations: [a] Alzheimer Disease Research Unit, CIEN Foundation, Carlos III Institute of Health, Alzheimer Center Reina Sofia Foundation, Madrid, Spain | [b] Hospital Puerta de Hierro, Servicio de Neurología, Madrid, Spain | [c] Hospital Universitario del Henares, Servicio de Medicina Interna, Madrid, Spain | [d] Chronic Disease Programme and CIBERNED, Carlos III Institute of Health, Madrid, Spain

Correspondence: [*] Correspondence to: Mª Ascensión Zea-Sevilla, MD, PhD, Alzheimer Disease Research Unit, CIEN Foundation, Carlos III Institute of Health, Alzheimer Center Reina Sofia Foundation, c/ Valderrebollo n°5, CP 28031, Madrid, Spain. E-mail: mazea@fundacioncien.es.

Abstract: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare inherited cerebrovascular disease associated with mutations in the NOTCH3 gene on chromosome 19, and represents the most common hereditary stroke disorder. We describe a pedigree, which suffered the classical clinical CADASIL pattern of migraine headaches, recurrent subcortical infarcts, and subcortical dementia, associated with a previously undescribed missense mutation (c.[244T>C], p.[C82R]) in NOTCH3. This new mutation extends the list of known pathogenic mutations responsible for CADASIL, which are associated with an odd number of cysteine residues within any of the epidermal growth factor-like repeats of Notch3 receptor protein.

Keywords: CADASIL, C82R, dementia, headache, migraine, NOTCH3 mutation, Notch3 receptor protein, stroke

DOI: 10.3233/JAD-141218

Journal: Journal of Alzheimer's Disease, vol. 43, no. 2, pp. 363-367, 2015