Genetic Testing in Brugada Syndrome: A 30-Year Experience.

IF 9.1 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Circulation. Arrhythmia and electrophysiology Pub Date : 2024-04-01 Epub Date: 2024-03-01 DOI:10.1161/CIRCEP.123.012374

Luigi Pannone, Antonio Bisignani, Randy Osei, Anaïs Gauthey, Antonio Sorgente, Cinzia Monaco, Domenico Giovanni Della Rocca, Alvise Del Monte, Antanas Strazdas, Joerelle Mojica, Maysam Al Housari, Vincenzo Miraglia, Sahar Mouram, Giampaolo Vetta, Gaetano Paparella, Robbert Ramak, Ingrid Overeinder, Gezim Bala, Alexandre Almorad, Erwin Ströker, Gudrun Pappaert, Juan Sieira, Thomy de Ravel, Mark La Meir, Andrea Sarkozy, Pedro Brugada, Gian Battista Chierchia, Sonia Van Dooren, Carlo de Asmundis

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引用次数: 0

Abstract

Background: A pathogenic/likely pathogenic variant can be found in 20% to 25% of patients with Brugada syndrome (BrS) and a pathogenic/likely pathogenic variant in SCN5A is associated with a worse prognosis. The aim of this study is to define the diagnostic yield of a large gene panel with American College of Medical Genetics and Genomics variant classification and to assess prognosis of SCN5A and non-SCN5A variants.

Methods: All patients with BrS, were prospectively enrolled in the Universitair Ziekenhuis Brussel registry between 1992 and 2022. Inclusion criteria for the study were (1) BrS diagnosis; (2) genetic analysis performed with a large gene panel; (3) classification of variants following American College of Medical Genetics and Genomics guidelines. Patients with a pathogenic/likely pathogenic variant in SCN5A were defined as SCN5A⁺. Patients with a reported variant in a non-SCN5A gene or with no reported variants were defined as patients with SCN5A^-. All variants were classified as missense or predicted loss of function.

Results: A total of 500 BrS patients were analyzed. A total of 104 patients (20.8%) were SCN5A⁺ and 396 patients (79.2%) were SCN5A^-. A non-SCN5A gene variant was found in 75 patients (15.0%), of whom, 58 patients (77.3%) had a missense variant and 17 patients (22.7%) had a predicted loss of function variant. At a follow-up of 84.0 months, 48 patients (9.6%) experienced a ventricular arrhythmia (VA). Patients without any variant had higher VA-free survival, compared with carriers of a predicted loss of function variant in SCN5A⁺ or non-SCN5A genes. There was no difference in VA-free survival between patients without any variant and missense variant carriers in SCN5A⁺ or non-SCN5A genes. At Cox analysis, SCN5A⁺ or non-SCN5A predicted loss of function variant was an independent predictor of VA.

Conclusions: In a large BrS cohort, the yield for SCN5A⁺ is 20.8%. A predicted loss of function variant carrier is an independent predictor of VA.

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Brugada 综合征的基因检测：30 年的经验

背景：20%至25%的布鲁格达综合征（BrS）患者可能存在致病性/可能致病性变异，而SCN5A的致病性/可能致病性变异与较差的预后有关。本研究的目的是根据 ACMG 变异分类确定大型基因面板的诊断率，并评估 SCN5A 和非 SCN5A 变异的预后：方法：1992 年至 2022 年间，所有 BrS 患者均在 UZB 登记处进行了前瞻性登记。研究的纳入标准为：（1）确诊为 BrS；（2）使用大型基因面板进行遗传分析；（3）根据 ACMG 指南对变异进行分类。SCN5A中存在致病/可能致病变异的患者被定义为SCN5A+。非 SCN5A 基因变异或无变异报告的患者被定义为 SCN5A- 患者。所有变异均被归类为错义或预测功能缺失：共分析了 500 名 BrS 患者。共有 104 名患者（20.8%）为 SCN5A+，396 名患者（79.2%）为 SCN5A-。在 75 名患者（15.0%）中发现了非 SCN5A 基因变异，其中 58 名患者（77.3%）为错义变异，17 名患者（22.7%）为预测功能缺失变异。在84.0个月的随访中，48名患者（9.6%）出现了室性心律失常（VA）。与SCN5A+或非SCN5A基因的预测功能缺失变异携带者相比，没有任何变异的患者无VA生存率更高。没有任何变异的患者与SCN5A+或非SCN5A基因的错义变异携带者之间的无VA生存率没有差异。在Cox分析中，SCN5A+或非SCN5A预测功能缺失变异是VA的独立预测因子：结论：在一个大型 BrS 队列中，SCN5A+ 的发病率为 20.8%。预测的功能缺失变异携带者是VA的独立预测因子。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Circulation. Arrhythmia and electrophysiology 医学-心血管系统

CiteScore

13.70

自引率

4.80%

发文量

187

审稿时长

4-8 weeks

期刊介绍： Circulation: Arrhythmia and Electrophysiology is a journal dedicated to the study and application of clinical cardiac electrophysiology. It covers a wide range of topics including the diagnosis and treatment of cardiac arrhythmias, as well as research in this field. The journal accepts various types of studies, including observational research, clinical trials, epidemiological studies, and advancements in translational research.