Genotype-phenotype correlations of cysteine replacement in CADASIL
Genotype-phenotype correlations of cysteine replacement in CADASIL
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DOI：
10.1016/j.neurobiolaging.2016.10.026
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发表时间：
2017-02-01
影响因子：
4.2
通讯作者：
Hattori, Nobutaka
中科院分区：
文献类型：
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作者：
Matsushima, Takashi;Conedera, Silvio;Hattori, Nobutaka
脑常染色体显性动脉病伴皮层下梗死和脑白质病（CADASIL）的特征是与notch同源蛋白3 （NOTCH3）突变相关的脑梗死。我们招募了10例脑磁共振成像（MRI）液体衰减反转恢复图像显示深部白质和外囊高强度（HIs）的患者。然后，我们在NOTCH3的2-24外显子的内含子-外显子边界区域内使用直接测序来研究NOTCH3的突变。8例患者携带NOTCH3突变（10例中的8例），包括一种新的突变，p.C162Y，以及3例散发形式。7例半胱氨酸替代患者在颞叶前部（ATLs）出现HI，而在1例未进行半胱氨酸替代的患者中未检测到这些变化，p.R75P。回顾以往的报道，我们得出结论，患者可以明确地分为两组：半胱氨酸替代患者在ATL中显示HI，未半胱氨酸替代患者在ATL中未显示HI。我们的研究结果扩大了对大脑常染色体显性动脉病变伴皮层下梗死和白质脑病的基因型-表型相关性的理解。(C) 2016 Elsevier Inc.版权所有。
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 genotypeephenotype correlations in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. (C) 2016 Elsevier Inc. All rights reserved.