Whole-Exome Sequencing Identifies a Novel Mutation of Desmocollin 2 in a Chinese Family With Arrhythmogenic Right Ventricular Cardiomyopathy
Whole-Exome Sequencing Identifies a Novel Mutation of Desmocollin 2 in a Chinese Family With Arrhythmogenic Right Ventricular Cardiomyopathy
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全外显子组测序鉴定出一个患有致心律失常性右心室心肌病的中国家族中桥粒胶蛋白 2 的新突变
DOI：
10.1016/j.amjcard.2017.01.011
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发表时间：
2017-05-01
影响因子：
2.8
通讯作者：
Xiang, Rong
中科院分区：
文献类型：
--
作者：
Liu, Ji-Shi;Fan, Liang-Liang;Xiang, Rong
心律失常性右室心肌病（ARVC）是一种罕见的心脏疾病，以心肌细胞丧失和纤维脂肪组织替代为特征。随着ARVC的进展，患者可出现严重的室性心律失常、心力衰竭，甚至心源性猝死。以往的研究表明，ARVC的产生和发展是一个复杂的过程。与桥粒结构改变有关。迄今为止，已在ARVC患者中发现了至少5种与桥粒相关的基因，包括桥粒蛋白、嗜血小板蛋白2、桥粒蛋白2、桥粒蛋白2和结蛋白。在这项研究中，我们应用全外显子组测序来探索可疑ARVC的中国家庭的潜在致病基因。一种新的错义突变（约1090年）g> A/p。确定了DSC2的V364 M)，并与受影响的家庭成员共同隔离。这种突变导致缬氨酸被蛋氨酸取代，并被生物信息学工具预测为破坏性的。总之，我们的研究不仅扩大了DSC2突变谱，有助于ARVC家庭的遗传咨询，而且提高了中国ARVC患者对发病机制的认识。(C) 2017爱思唯尔公司版权所有。
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare heart disorder characterized by myocyte loss and fibro-fatty tissue replacement. With the progress of ARVC, patient can present serious ventricular arrhythmias, heart failure, and even sudden cardiac death. Previous studies have revealed that the generation and development of ARVC are. related to structural changes of desmosomes. To date, at least 5 genes associated with desmosomes have been identified in patients with ARVC, including Desmoplakin, Plakophilin 2, Destrzoglein 2, Desmocollin 2, and Junction plakoglobin. In this study, we applied whole-exome sequencing to explore the potential causative gene in a Chinese family with suspicious ARVC. A novel missense mutation (c.1090 G > A/p.V364 M) of DSC2 was identified and co-segregated with the affected family members. This mutation leads to a substitution of valine by methionine and is predicted to be damaging by bioinformatics tools. In conclusion, our study not only expands the spectrum of DSC2 mutations and contributes to genetic counseling of families with ARVC but also improves the awareness of pathogenesis in Chinese patients with ARVC. (C) 2017 Elsevier Inc. An rights reserved.