Mutation Spectrum in a Large Cohort of Unrelated Chinese Patients With Hypertrophic Cardiomyopathy
Mutation Spectrum in a Large Cohort of Unrelated Chinese Patients With Hypertrophic Cardiomyopathy
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大量无血缘关系的中国肥厚型心肌病患者的突变谱
DOI：
10.1016/j.amjcard.2013.04.021
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发表时间：
2013-08-15
影响因子：
2.8
通讯作者：
Tong, Qiguang
中科院分区：
文献类型：
--
作者：
Liu, Wen;Liu, Wenling;Tong, Qiguang
肥厚型心肌病(HC)是一种遗传性异质性心血管疾病。现有的数据主要是高加索人的样本，需要在中国人口中进行大规模研究。本研究旨在探讨中国人群中不同基因型别的遗传基础和临床特征。对136例无血缘关系的中国HC患者进行了β-肌球蛋白重链(MYH7)、肌球蛋白结合蛋白C(MYBPC3)和心肌肌钙蛋白T(TNNT2)基因直接测序。并进行临床评价。总共在36名患者(27%)中发现了32个突变，其中包括10个新的突变。突变频率分别为56%(MYBPC3)、31%(MYH7)和13%(TNNT2)。在3%的患者中发现了双突变。HC相关肌节突变的发生与发病年龄较早、左心室肥厚增加、晕厥发生率较高、既往家族史有关。和心源性猝死。携带MYBPC3和MYH7突变的患者在临床特征和预后方面没有统计学差异。在这项研究中，具有双突变的患者与恶性进展有关。结论：MYBPC3基因是HC最主要的优势基因。在MYH7、MYBPC3和TNNT2中，多重突变是常见的。目前的研究表明，HC具有很大的多样性，而且基因型对预后有一定的预测作用。(C)2013 Elsevier Inc.保留所有权利。
Hypertrophic cardiomyopathy (HC) is a hereditary heterogeneous cardiovascular disorder. Existing data have been of predominantly Caucasian samples, and a large study is needed in Chinese population. The present study was intended to explore the genetic basis and clinical characteristics correlated with different genotypes in a large cohort of Chinese patients. Direct gene sequencing of beta-myosin heavy chain (MYH7), myosin binding protein-C (MYBPC3), and cardiac troponin T (TNNT2) was performed in 136 unrelated Chinese HC patients. Clinical evaluations were conducted. In total, 32 mutations were identified in 36 patients (27%), including 10 novel ones. Distribution of mutations was 56% (MYBPC3), 31% (MYH7), and 13% (TNNT2), respectively. Double mutations were identified in 3% patients. The occurrence of HC-associated sarcomeric mutations was associated with an earlier age of onset, increased left ventricular hypertrophy, a higher incidence of syncope, previous family history,. and sudden cardiac death. No statistical difference was identified in patients carrying MYBPC3 and MYH7 mutations with regard to clinical characteristics and outcomes. Patients with double mutations were associated with malignant progression in the study. In conclusion, MYBPC3 is the most predominant gene in HC. Multiple mutations are common in MYH7, MYBPC3, and TNNT2. The present study suggests a large diversity of HC and a prognostic role of genotype. (C) 2013 Elsevier Inc. All rights reserved.