Genotype-phenotype correlations of cysteine replacement in CADASIL

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• 作者：Takashi Matsushima^a ; Silvio Conedera^a ; Ryota Tanaka^a ; Yuanzhe Li^a ; Hiroyo Yoshino^b ; Manabu Funayama^a ; ^b ; Aya Ikeda^a ; Yuka Hosaka^a ; Ayame Okuzumi^a ; Yoshiaki Shimada^a ; Kazuo Yamashiro^a ; Yumiko Motoi^a ; Kenya Nishioka^a ; Nobutaka Hattori^a ; ^b ; ^{nhattori@juntendo.ac.jp}
• 关键词：CADASIL ; NOTCH3 ; Hereditary leukoaraiosis ; Genetics
• 刊名：Neurobiology of Aging
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：50
• 期：Complete
• 页码：169.e7-169.e14
• 全文大小：1157 K
• 卷排序：50

文摘

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.