Brugada 综合征中 SCN5A 的拷贝数变异。

Copy number variations of SCN5A in Brugada syndrome.

机构信息

Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Department of Molecular Biology, National Cerebral and Cardiovacular Center, Suita, Japan.

Department of Molecular Biology, National Cerebral and Cardiovacular Center, Suita, Japan; Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan; Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan.

出版信息

Heart Rhythm. 2018 Aug;15(8):1179-1188. doi: 10.1016/j.hrthm.2018.03.033. Epub 2018 Mar 21.

DOI:10.1016/j.hrthm.2018.03.033

PMID:29574140

Abstract

BACKGROUND

Loss-of-function mutations in SCN5A are associated in ∼20% of Brugada syndrome (BrS) patients. Copy number variations (CNVs) have been shown to be associated with several inherited arrhythmia syndromes.

OBJECTIVE

The purpose of this study was to investigate SCN5A CNVs among BrS probands.

METHODS

The study cohort consisted of 151 BrS probands who were symptomatic or had a family history of BrS, sudden death, syncope, or arrhythmic diseases. We performed sequence analysis of SCN5A by the Sanger method. For detecting CNVs in SCN5A, we performed multiplex ligation-dependent probe amplification analysis of the 151 BrS probands.

RESULTS

We identified pathogenic SCN5A mutations in 20 probands by the Sanger method. In 140 probands in whom multiplex ligation-dependent probe amplification was successfully performed, 4 probands were found to present different CNVs (deletion in 3 and duplication in 1). Three of them had fatal arrhythmia events; the remaining 1 was asymptomatic but had a family history. Mean age at diagnosis was 23 ± 14 years. All of the baseline 12-lead electrocardiograms showed PQ-interval prolongation. The characteristics of these 4 probands with CNVs were similar to those of the probands with mutations leading to premature truncation of the protein or missense mutations causing peak I reduction >90%.

CONCLUSION

We identified SCN5A CNVs in 2.9% of BrS probands who were symptomatic or had a family history.

摘要

背景

SCN5A 的功能丧失性突变与大约 20%的 Brugada 综合征 (BrS) 患者相关。拷贝数变异 (CNVs) 已被证明与几种遗传性心律失常综合征相关。

目的

本研究旨在研究 BrS 先证者中的 SCN5A CNVs。

方法

研究队列包括 151 名有症状或有 BrS、猝死、晕厥或心律失常病史的 BrS 先证者。我们通过 Sanger 法对 SCN5A 进行序列分析。为了检测 SCN5A 中的 CNVs，我们对 151 名 BrS 先证者进行了多重连接依赖性探针扩增分析。

结果

我们通过 Sanger 法在 20 名先证者中鉴定出致病性 SCN5A 突变。在 140 名成功进行多重连接依赖性探针扩增的先证者中，发现 4 名先证者存在不同的 CNVs（3 名缺失，1 名重复）。其中 3 人发生致命性心律失常事件；其余 1 人无症状，但有家族史。诊断时的平均年龄为 23 ± 14 岁。所有基线 12 导联心电图均显示 PQ 间期延长。这 4 名存在 CNVs 的先证者的特征与那些导致蛋白质提前截断或峰 I 减少>90%的错义突变的先证者相似。