{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:27:51Z","timestamp":1792290471952,"version":"4.4.0"},"reference-count":143,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T00:00:00Z","timestamp":1688515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Brugada syndrome is a rare hereditary arrhythmia disorder characterized by a distinctive electrocardiogram pattern and an elevated risk of ventricular arrhythmias and sudden cardiac death in young adults. Despite recent advances, it remains a complex condition, encompassing mechanisms, genetics, diagnosis, arrhythmia risk stratification, and management. The underlying electrophysiological mechanism of Brugada syndrome requires further investigation, with current theories focusing on abnormalities in repolarization, depolarization, and current-load match. The genetic basis of the syndrome is strong, with mutations found in genes encoding subunits of cardiac sodium, potassium, and calcium channels, as well as genes involved in channel trafficking and regulation. While the initial discovery of mutations in the SCN5A gene provided valuable insights, Brugada syndrome is now recognized as a multifactorial disease influenced by several loci and environmental factors, challenging the traditional autosomal dominant inheritance model. This comprehensive review aims to provide a current understanding of Brugada syndrome, focusing on its pathophysiology, genetic mechanisms, and novel models of risk stratification. Advancements in these areas hold the potential to facilitate earlier diagnosis, improve risk assessments, and enable more targeted therapeutic interventions.<\/jats:p>","DOI":"10.3390\/cells12131791","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:34:30Z","timestamp":1688603670000},"page":"1791","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Genetic and Molecular Mechanisms in Brugada Syndrome"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5677-7391","authenticated-orcid":false,"given":"Errol","family":"Moras","sequence":"first","affiliation":[{"name":"Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kruti","family":"Gandhi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharat","family":"Narasimhan","sequence":"additional","affiliation":[{"name":"Debakey Cardiovascular Institute, Houston Methodist Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Brugada","sequence":"additional","affiliation":[{"name":"Cardiology, Cardiac Genetics Clinical Unit, Hospital Universitari Josep Trueta, Hospital Santa Caterina, 17007 Girona, Spain"},{"name":"Cardiovascular Genetics Center and Clinical Diagnostic Laboratory, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Girona-IdIBGi, 17190 Salt, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Brugada","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Pediatric Arrhythmia Unit, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Department of Medicine, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Brugada","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Free University of Brussels (UZ Brussel) VUB, B-1050 Brussels, Belgium"},{"name":"Medical Centre Prof. Brugada, B-9300 Aalst, Belgium"},{"name":"Arrhythmia Unit, Helicopteros Sanitarios Hospital (HSH), Puerto Ban\u00fas, 29603 Marbella, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chayakrit","family":"Krittanawong","sequence":"additional","affiliation":[{"name":"Cardiology Division, NYU Langone Health and NYU School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1016\/0735-1097(92)90253-J","article-title":"Right bundle branch block, persistent ST segment elevation and sudden cardiac death: A distinct clinical and electrocardiographic syndrome: A multicenter report","volume":"20","author":"Brugada","year":"1992","journal-title":"J. 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