title: Arg332Cys mutation of NOTCH3 gene in the first known Taiwanese family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
abstract: The phenotype and genotype of cerebral autosomal dominant arteriopathy and subcortical infarcts and leukoencephalopathy (CADASIL) in Caucasians have been well characterized, but CADASIL is less recognized in Asian populations. Here we investigated the first known Taiwanese family affected by CADASIL and identified an uncommon NOTCH3 mutation. The family had clinical manifestations in affected members including recurrent strokes, early dementia, and depression, but not migraine. A skin biopsy in the proband patient showed characteristic pathological findings of CADASIL on electron microscopy. Afterward, genetic analysis found an Arg332Cys mutation at exon 6 of NOTCH3. Neuropsychological evaluation showed vascular dementia in two of four affected people. Head MRI showed multiple infarcts in bilateral basal ganglia, thalami, periventricular white matter, external capsules, and brainstem, but involvement of the anterior temporal pole was found only in two people with milder symptoms. To our knowledge, the Arg332Cys NOTCH3 mutation at exon 6, which was identified in the studied family, has not been reported in Asian populations. Our findings emphasize the importance of genetic analysis of NOTCH3 for Asians with a phenotype typical of CADASIL.
authors.affiliation: Stroke Center, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Sung-Chun
authors.initials: SC
authors.lastname: Tang
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Lee
authors.forename: Jiann-Shing
authors.initials: JS
authors.lastname: Jeng
authors.forename: Ping-Keung
authors.initials: PK
authors.lastname: Yip
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D044466:Asian People; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D046589:CADASIL / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D002681:China / Q000208:ethnology; D004252:DNA Mutational Analysis; D003704:Dementia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D003866:Depressive Disorder / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D005091:Exons / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface / Q000235:genetics*; D051880:Receptors, Notch; D012867:Skin / Q000473:pathology / Q000648:ultrastructure; D020521:Stroke / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D013624:Taiwan / Q000453:epidemiology
chemical_list: C499374:NOTCH3 protein, human; D011518:Proto-Oncogene Proteins; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface; D051880:Receptors, Notch