{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T11:48:13Z","timestamp":1776944893464,"version":"3.51.4"},"reference-count":38,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T00:00:00Z","timestamp":1731628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Inherited cardiac channelopathies are major causes of sudden cardiac death (SCD) in young people. Genetic testing is focused on the identification of single-nucleotide variants (SNVs) by Next-Generation Sequencing (NGS). However, genetically elusive cases can carry copy number variants (CNVs), which need specific detection tools. We underlie the utility of identifying CNVs by investigating the literature data and internally analyzing cohorts with CNVs in KCNQ1, KCNH2, SCN5A, and RYR2. CNVs were reported in 119 patients from the literature and 21 from our cohort. Young patients with CNVs in KCNQ1 show a Long QT (LQT) phenotype &gt; 480 ms and a higher frequency of syncope. None of them had SCD. All patients with CNV in KCNH2 had a positive phenotype for QT &gt; 480 ms. CNVs in SCN5A were represented by the Brugada pattern, with major cardiac events mainly in males. Conversely, adult females show more supraventricular arrhythmias. RYR2-exon3 deletion showed a broader phenotype, including left ventricular non-compaction (LVNC) and catecholaminergic polymorphic ventricular tachycardia (CPVT). Pediatric patients showed atrial arrhythmias and paroxysmal atrial fibrillation. Relatively higher syncope and SCA were observed in young females. The detection of CNVs can be of greater yield in two groups: familial channelopathies and patients with suspected Jervell and Lange-Nielsen syndrome or CPVT. The limited number of reported individuals makes it mandatory for multicentric studies to give future conclusive results.<\/jats:p>","DOI":"10.3390\/biom14111450","type":"journal-article","created":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T08:28:13Z","timestamp":1731659293000},"page":"1450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Copy Number Variants in Cardiac Channelopathies: Still a Missed Part in Routine Arrhythmic Diagnostics"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0764-686X","authenticated-orcid":false,"given":"Maria","family":"Gnazzo","sequence":"first","affiliation":[{"name":"Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2275-9670","authenticated-orcid":false,"given":"Giovanni","family":"Parlapiano","sequence":"additional","affiliation":[{"name":"Cardiogenetic Center, Rare Diseases and Medical Genetics Units, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Di Lorenzo","sequence":"additional","affiliation":[{"name":"Cardiogenetic Center, Rare Diseases and Medical Genetics Units, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7561-7406","authenticated-orcid":false,"given":"Daniele","family":"Perrino","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5514-5018","authenticated-orcid":false,"given":"Silvia","family":"Genovese","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Lanari","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Righi","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology and Arrhythmia\/Syncope Complex Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Cal\u00ec","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology and Arrhythmia\/Syncope Complex Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9284-5972","authenticated-orcid":false,"given":"Massimo Stefano","family":"Silvetti","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology and Arrhythmia\/Syncope Complex Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Falcone","sequence":"additional","affiliation":[{"name":"Biogenet, Medical and Forensic Genetics Laboratory, 87100 Cosenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Bauleo","sequence":"additional","affiliation":[{"name":"Biogenet, Medical and Forensic Genetics Laboratory, 87100 Cosenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1888-373X","authenticated-orcid":false,"given":"Fabrizio","family":"Drago","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology and Arrhythmia\/Syncope Complex Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"},{"name":"The European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9037-4297","authenticated-orcid":false,"given":"Antonio","family":"Novelli","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anwar","family":"Baban","sequence":"additional","affiliation":[{"name":"Cardiogenetic Center, Rare Diseases and Medical Genetics Units, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"},{"name":"The European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1016\/j.hrthm.2013.05.014","article-title":"HRS\/EHRA\/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients with Inherited Primary Arrhythmia Syndromes: Document Endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013","volume":"10","author":"Priori","year":"2013","journal-title":"Heart 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