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
{"title":"Brugada 综合征的基因检测：30 年的经验","authors":"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","doi":"10.1161/CIRCEP.123.012374","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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<sup>+</sup>. Patients with a reported variant in a <i>non-SCN5A</i> gene or with no reported variants were defined as patients with SCN5A<sup>-</sup>. All variants were classified as missense or predicted loss of function.</p><p><strong>Results: </strong>A total of 500 BrS patients were analyzed. A total of 104 patients (20.8%) were SCN5A<sup>+</sup> and 396 patients (79.2%) were SCN5A<sup>-</sup>. A <i>non-SCN5A</i> 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 <i>SCN5A<sup>+</sup></i> or <i>non-SCN5A</i> genes. There was no difference in VA-free survival between patients without any variant and missense variant carriers in <i>SCN5A<sup>+</sup></i> or <i>non-SCN5A</i> genes. At Cox analysis, SCN5A<sup>+</sup> or non-SCN5A predicted loss of function variant was an independent predictor of VA.</p><p><strong>Conclusions: </strong>In a large BrS cohort, the yield for SCN5A<sup>+</sup> is 20.8%. A predicted loss of function variant carrier is an independent predictor of VA.</p>","PeriodicalId":10319,"journal":{"name":"Circulation. Arrhythmia and electrophysiology","volume":" ","pages":"e012374"},"PeriodicalIF":9.1000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genetic Testing in Brugada Syndrome: A 30-Year Experience.\",\"authors\":\"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\",\"doi\":\"10.1161/CIRCEP.123.012374\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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<sup>+</sup>. Patients with a reported variant in a <i>non-SCN5A</i> gene or with no reported variants were defined as patients with SCN5A<sup>-</sup>. All variants were classified as missense or predicted loss of function.</p><p><strong>Results: </strong>A total of 500 BrS patients were analyzed. A total of 104 patients (20.8%) were SCN5A<sup>+</sup> and 396 patients (79.2%) were SCN5A<sup>-</sup>. A <i>non-SCN5A</i> 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 <i>SCN5A<sup>+</sup></i> or <i>non-SCN5A</i> genes. There was no difference in VA-free survival between patients without any variant and missense variant carriers in <i>SCN5A<sup>+</sup></i> or <i>non-SCN5A</i> genes. At Cox analysis, SCN5A<sup>+</sup> or non-SCN5A predicted loss of function variant was an independent predictor of VA.</p><p><strong>Conclusions: </strong>In a large BrS cohort, the yield for SCN5A<sup>+</sup> is 20.8%. A predicted loss of function variant carrier is an independent predictor of VA.</p>\",\"PeriodicalId\":10319,\"journal\":{\"name\":\"Circulation. Arrhythmia and electrophysiology\",\"volume\":\" \",\"pages\":\"e012374\"},\"PeriodicalIF\":9.1000,\"publicationDate\":\"2024-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Circulation. Arrhythmia and electrophysiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1161/CIRCEP.123.012374\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/3/1 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Circulation. Arrhythmia and electrophysiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1161/CIRCEP.123.012374","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/1 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Genetic Testing in Brugada Syndrome: A 30-Year Experience.
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.
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.
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