{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T14:54:59Z","timestamp":1758293699341,"version":"3.44.0"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cardiovasc electrophysiol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Genetic mutations involving sodium channel Nav 1.5 have been linked with Brugada Syndrome (BrS). Caveolin\u20103(CAV\u20103) is a protein that could modulate Nav1.5 function. Aim of the study is to characterize a multi\u2010generational family with BrS and <jats:italic>CAV\u20103<\/jats:italic> gene mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>Clinical and genetic investigations were performed. Genetic testing was performed with whole\u2010exome sequencing (WES). Variants found by WES were evaluated in all family members by bidirectional capillary Sanger resequencing. The effect of the mutation was investigated by using in <jats:italic>silico<\/jats:italic> prediction of pathogenicity. Index case was a 58\u2010year\u2010old man with BrS, that needed an implantable cardioverter defibrillator (ICD) due to resuscitated cardiac arrest. WES of the index case identified a missense mutation p.(Thr78Met) of the <jats:italic>CAV3<\/jats:italic> gene and two additionally variants: <jats:italic>ADRB1<\/jats:italic> p.(Leu353Met) and <jats:italic>GRK5<\/jats:italic> p.(Thr129Met). Six out of 11 family members had BrS ECG and were all CAV\u20103 mutation carriers. Three family members had CAV\u20103 mutation and ADRB1 and GRK5 variants. ICD implant was needed in four family members. All patients with CAV\u20103, ADRB1 and GRK5 gene mutations underwent ICD implant due to cardiac arrest or arrhythmic syncope. Another patient with CAV\u20103 mutation only, had and ICD implant due to spontaneous BrS type 1 ECG and positive electrophysiological study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Caveolin 3 p.(Thr78Met) gene mutation could be associated with BrS. This mutation if combined with other susceptible BrS gene variations as <jats:italic>ADRB1<\/jats:italic> p.(Leu353Met) and <jats:italic>GRK5<\/jats:italic> p.(Thr129Met), could have an increased arrhythmic risk.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jce.16770","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T08:50:08Z","timestamp":1750668608000},"page":"2132-2139","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Caveolin 3 Variant T78M in a Large Family With Brugada Syndrome: Clinical Features and Coexistence of ADRB1 and GRK5 Gene Mutation"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9909-6513","authenticated-orcid":false,"given":"Francesco","family":"Santoro","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences University of Foggia Foggia Italy"},{"name":"Cardiology Unit, University Hospital 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Foggia Foggia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna","family":"D'Andrea","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Clinical and Experimental Medicine University of Foggia Foggia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2961-2783","authenticated-orcid":false,"given":"PierLuigi","family":"Pellegrino","sequence":"additional","affiliation":[{"name":"Cardiology Unit, University Hospital \u201cPoliclinico\u201d of Foggia Foggia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Mazzanti","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Molecular Cardiology, IRCCS Istituti Clinici Scientifici Maugeri University of Pavia Pavia  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