The genetic spectrum and the evaluation of CADASIL screening scale in Chinese patients with NOTCH3 mutations
The genetic spectrum and the evaluation of CADASIL screening scale in Chinese patients with NOTCH3 mutations
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中国NOTCH3突变患者基因谱及CADASIL筛查量表评价
DOI：
10.1016/j.jns.2015.04.047
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发表时间：
2015-07-15
影响因子：
4.4
通讯作者：
Wang, Zhaoxia
中科院分区：
文献类型：
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作者：
Liu, Xiao;Zuo, Yuehuan;Wang, Zhaoxia
伴有皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病（CADASIL）是一种由NOTCH 3基因突变引起的遗传性小动脉疾病。本文报道了29例新诊断的CADASIL患者的临床、病理和遗传学特征，CADASIL量表在中国CADASIL患者中的评价，以及对所有已报告的中国大陆NOTCH 3基因突变患者的再分析。我们发现两个新的突变（p.C134G和p.C291Y）和13个报告的NOTCH 3突变在新诊断的组。在53例中国NOTCH 3突变患者中，19例CADASIL量表评分低于临界评分，敏感性仅为64.1%。在研究时，遗传学确诊的CADASIL病例总数达到158例，来自97个无关的中国大陆家庭，其中9/97（9.3%）为散发患者。NOTCH 3基因突变谱显示43个突变，热点在外显子4，其次是外显子3。携带相同NOTCH 3错义突变的患者的发病年龄和CADASIL量表评分存在相当大的变异性，表明表型-基因型无明显相关性。总之，我们报告了两个新的突变，扩大了NOTCH 3突变谱。外显子4和3是中国大陆NOTCH 3突变的热点。CADASIL量表在中国人群中的敏感性较低，提示CADASIL量表在中国人群中使用时应根据中国CADASIL患者的临床特点进行完善。(C)2015 Elsevier B. V.版权所有。
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small artery disease caused by NOTCH3 gene mutation. Here we report clinical, pathological and genetic profiles of 29 newly-diagnosed CADASIL patients, evaluation of the CADASIL scale in Chinese CADASIL patients, and reanalysis of all reported mainland Chinese patients with identified NOTCH3 gene mutation. We found two novel mutations (p.C134G and p.C291Y) and 13 reported NOTCH3 mutations in the newly-diagnosed group. CADASIL scale score was less than the cutoff score in 19 of 53 Chinese patients with NOTCH3 mutation, generating only a sensitivity of 64.1%. At the time of study, the total number of genetically confirmed CADASIL cases reached 158 from 97 unrelated mainland Chinese families, with 9/97 (9.3%) sporadic patients. The NOTCH3 gene mutation profile showed 43 mutations, with hotspots in exon 4, followed by exon 3. The considerable variability in onset age and CADASIL scale score in patients carrying the same NOTCH3 missense mutation suggested no obvious phenotype-genotype correlation. In conclusion, we report two novel mutations which expand the NOTCH3 mutational spectrum. Exons 4 and 3 are hotspots in mainland Chinese patients with NOTCH3 mutation. The low sensitivity of CADASIL scale in our patients group indicated that the CADASIL scale should be refined according to the clinical characteristics of Chinese CADASIL patients when used in Chinese populations. (C) 2015 Elsevier B.V. All rights reserved.