title: CADASIL with a novel NOTCH3 mutation (Cys478Tyr).
abstract: Recently, an increasing number of NOTCH3 mutations have been described to cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Here, we report 2 CADASIL patients from a Japanese family, who were found to possess a novel NOTCH3 mutation. The proband only had chronic headache, and her mother had previously suffered a minor stroke. Although the patients' clinical symptoms were mild, their distinctive magnetic resonance imaging (MRI) features suggested CADASIL. Genetic analysis revealed that both patients had a novel heterozygous NOTCH3 mutation (p.Cys478Tyr) leading to stereotypical cysteine loss. The present finding suggests that genetic testing for NOTCH3 mutations in patients with distinctive MRI features, even if the symptoms are as mild as chronic headache, should help to broaden the mutational and clinical spectrum of CADASIL.
authors.affiliation: Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: k-oznuro@tmd.ac.jp.
authors.forename: Kokoro
authors.initials: K
authors.lastname: Ozaki
authors.affiliation: Department of Neurology, Yokosuka Kyosai Hospital, Yokosuka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Irioka
authors.affiliation: Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kinya
authors.initials: K
authors.lastname: Ishikawa
authors.affiliation: Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Mizusawa
mesh_terms: D000368:Aged; D046589:CADASIL / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D020773:Headache Disorders / Q000175:diagnosis / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011237:Predictive Value of Tests; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000235:genetics
chemical_list: C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch
keywords: C478Y; CADASIL; Cys478Tyr; NOTCH3; cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; mutation