title: Genotype-phenotype correlations of cysteine replacement in CADASIL.
abstract: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by cerebral infarction related to mutations in the notch homolog protein 3 (NOTCH3). We enrolled 10 patients whose brain magnetic resonance imaging (MRI) fluid-attenuated inversion recovery images showed hyperintensities (HIs) in the deep white matter and the external capsule. We then investigated the mutations in NOTCH3 using direct sequencing within the region of intron-exon boundaries in exons 2-24 of NOTCH3. Eight patients harboring NOTCH3 mutations (8 of 10) were identified, including a novel mutation, p.C162Y, and 3 cases with a sporadic form. Seven patients with cysteine replacement showed HI in the anterior part of the temporal lobes (ATLs), whereas these changes were not detected in 1 patient without cysteine replacement, p.R75P. Reviewing previous reports, we conclude that the patients can clearly be divided in 2 groups: those with cysteine replacement who showed HI in the ATL and those without cysteine replacement who showed no HI in the ATL. Our findings expand the understanding of genotype-phenotype correlations in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsushima
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Silvio
authors.initials: S
authors.lastname: Conedera
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Tanaka
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yuanzhe
authors.initials: Y
authors.lastname: Li
authors.affiliation: Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Yoshino
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Funayama
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Ikeda
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Hosaka
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Ayame
authors.initials: A
authors.lastname: Okuzumi
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamashiro
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Motoi
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Kenya
authors.initials: K
authors.lastname: Nishioka
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan. Electronic address: nhattori@juntendo.ac.jp.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
mesh_terms: D000328:Adult; D000368:Aged; D046589:CADASIL / Q000000981:diagnostic imaging / Q000235:genetics*; D003545:Cysteine / Q000235:genetics*; D005091:Exons / Q000235:genetics; D066271:External Capsule / Q000000981:diagnostic imaging; D005260:Female; D005799:Genes, Dominant; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059906:Neuroimaging; D010641:Phenotype; D000071656:Receptor, Notch3 / Q000235:genetics; D066127:White Matter / Q000000981:diagnostic imaging
chemical_list: C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D003545:Cysteine
keywords: CADASIL; Genetics; Hereditary leukoaraiosis; NOTCH3