Brugada综合征中新型SCN5A单核苷酸变异的鉴定：一项来自香港的全地区研究。
Identification of Novel SCN5A Single Nucleotide Variants in Brugada Syndrome: A Territory-Wide Study From Hong Kong.
作者信息
Tse Gary, Lee Sharen, Liu Tong, Yuen Ho Chuen, Wong Ian Chi Kei, Mak Chloe, Mok Ngai Shing, Wong Wing Tak
机构信息
Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, China.
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China.
出版信息
Front Physiol. 2020 Sep 18;11:574590. doi: 10.3389/fphys.2020.574590. eCollection 2020.
BACKGROUND
The aim of this study is to report on the genetic composition of Brugada syndrome (BrS) patients undergoing genetic testing in Hong Kong.
METHODS
Patients with suspected BrS who presented to the Hospital Authority of Hong Kong between 1997 and 2019, and underwent genetic testing, were analyzed retrospectively.
RESULTS
A total of 65 subjects were included ( = 65, 88% male, median presenting age 42 [30-54] years old, 58% type 1 pattern). Twenty-two subjects (34%) showed abnormal genetic test results, identifying the following six novel, pathogenic or likely pathogenic mutations in SCN5A: c.674G > A, c.2024-11T > A, c.2042A > C, c.4279G > T, c.5689C > T, c.429del. Twenty subjects (31%) in the cohort suffered from spontaneous ventricular tachycardia/ventricular fibrillation (VT/VF) and 18 (28%) had incident VT/VF over a median follow-up of 83 [Q1-Q3: 52-112] months. Univariate Cox regression demonstrated that syncope (hazard ratio [HR]: 4.27 [0.95-19.30]; = 0.059), prior VT/VF (HR: 21.34 [5.74-79.31; < 0.0001) and T-wave axis (HR: 0.970 [0.944-0.998]; = 0.036) achieved < 0.10 for predicting incident VT/VF. After multivariate adjustment, only prior VT/VF remained a significant predictor (HR: 12.39 [2.97-51.67], = 0.001).
CONCLUSION
This study identified novel mutations in SCN5A in a Chinese cohort of BrS patients.
背景
本研究旨在报告香港接受基因检测的 Brugada 综合征（BrS）患者的基因组成情况。
方法
对 1997 年至 2019 年间到香港医院管理局就诊且接受基因检测的疑似 BrS 患者进行回顾性分析。
结果
共纳入 65 名受试者（n = 65，88%为男性，中位就诊年龄 42[30 - 54]岁，58%为 1 型心电图模式）。22 名受试者（34%）基因检测结果异常，在 SCN5A 基因中鉴定出以下六个新的、致病或可能致病的突变：c.674G > A、c.2024 - 11T > A、c.2042A > C、c.4279G > T、c.5689C > T、c.429del。队列中的 20 名受试者（31%）发生过自发性室性心动过速/心室颤动（VT/VF），18 名受试者（28%）在中位随访 83[第一四分位数 - 第三四分位数：52 - 112]个月期间发生过 VT/VF。单因素 Cox 回归分析显示，晕厥（风险比[HR]：4.27[0.95 - 19.30]；P = 0.059）、既往 VT/VF（HR：21.34[5.74 - 79.31]；P < 0.0001）和 T 波电轴（HR：0.970[0.944 - 0.998]；P = 0.036）在预测 VT/VF 发生方面 P < 0.10。多因素调整后，仅既往 VT/VF 仍是显著的预测因素（HR：12.39[2.97 - 51.67]，P = 0.001）。
结论
本研究在中国 BrS 患者队列中鉴定出 SCN5A 基因的新突变。
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