Genetic Basis and Genotype-Phenotype Correlations in Han Chinese Patients with Idiopathic Dilated Cardiomyopathy
Genetic Basis and Genotype-Phenotype Correlations in Han Chinese Patients with Idiopathic Dilated Cardiomyopathy
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DOI：
10.1038/s41598-020-58984-7
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发表时间：
2020-02-10
影响因子：
4.6
通讯作者：
Xu, Biao
中科院分区：
文献类型：
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作者：
Zhang, Xin-Lin;Xie, Jun;Xu, Biao
扩张型心肌病（DCM）是导致心力衰竭的主要原因之一。很大一部分遗传原因仍然无法解释，特别是在特发性DCM中。我们对118例汉族特发性DCM患者的心肌病和通道病的已知病因或候选基因进行了102个目标下一代测序。118例患者中有41例携带40种致病性或可能致病性变异，34.7%的患者提供了分子诊断。这些变体中有32种是新颖的。TTN截断变异占主导地位，频率为31.0%，其次是LMNA变异（14.3%）、RBM20变异（4.8%）和NEXN变异（4.8%）。这4个基因占鉴定的变异的一半以上。致病性或可能致病性变异携带者与非携带者（风险比1.11,95% CI: 0.41 - 3.00）、TTN截断变异患者与非TTN截断变异患者（风险比0.49,95% CI: 0.36 - 6.10）的临床特征或达到复合终点（心脏移植和心脏原因死亡）的比率无显著差异。在我们的前瞻性研究中，我们首先确定了汉族特发性DCM患者的总体遗传谱和基因型-表型相关性，这可以为该人群的DCM遗传诊断提供见解。
Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure. A large proportion of genetic cause remains unexplained, especially in idiopathic DCM. We performed target next-generation sequencing of 102 genes which were known causes or candidate genes for cardiomyopathies and channelpathies in 118 prospectively recruited Han Chinese patients with idiopathic DCM. 41 of the 118 patients carried 40 pathogenic or likely pathogenic variants, providing a molecular diagnosis in 34.7% of patients. 32 of these variants were novel. TTN truncating variants were predominant, with a frequency of 31.0%, followed by variants of LMNA (14.3%), RBM20 (4.8%), and NEXN (4.8%). These 4 genes accounted for over half variants identified. No significant difference in clinical characteristics or rates of reaching the composite end point (cardiac transplantation and death from cardiac causes) between pathogenic or likely pathogenic variant carriers and noncarriers (hazard ratio 1.11, 95% CI: 0.41 to 3.00), or between patients with TTN truncating variants or without (hazard ratio 0.49, 95% CI: 0.36 to 6.10). In our prospective study, we first determined the overall genetic profiles and genotype-phenotype correlations in Han Chinese idiopathic DCM patients, which could provide insight for genetic diagnosis of DCM in this population.