Copy Number Variants in Cardiac Channelopathies: Still a Missed Part in Routine Arrhythmic Diagnostics
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...
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MDPI AG
2024-11-01
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| author | Maria Gnazzo Giovanni Parlapiano Francesca Di Lorenzo Daniele Perrino Silvia Genovese Valentina Lanari Daniela Righi Federica Calì Massimo Stefano Silvetti Elena Falcone Alessia Bauleo Fabrizio Drago Antonio Novelli Anwar Baban |
| author_facet | Maria Gnazzo Giovanni Parlapiano Francesca Di Lorenzo Daniele Perrino Silvia Genovese Valentina Lanari Daniela Righi Federica Calì Massimo Stefano Silvetti Elena Falcone Alessia Bauleo Fabrizio Drago Antonio Novelli Anwar Baban |
| author_sort | Maria Gnazzo |
| collection | DOAJ |
| description | 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 <i>KCNQ1</i>, <i>KCNH2</i>, <i>SCN5A,</i> and <i>RYR2</i>. CNVs were reported in 119 patients from the literature and 21 from our cohort. Young patients with CNVs in <i>KCNQ1</i> show a Long QT (LQT) phenotype > 480 ms and a higher frequency of syncope. None of them had SCD. All patients with CNV in <i>KCNH2</i> had a positive phenotype for QT > 480 ms. CNVs in <i>SCN5A</i> were represented by the Brugada pattern, with major cardiac events mainly in males. Conversely, adult females show more supraventricular arrhythmias. <i>RYR2</i>-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. |
| format | Article |
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| institution | OA Journals |
| issn | 2218-273X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| series | Biomolecules |
| spelling | doaj-art-b3bd4e44dfc84444b67c1e1bd3874d3b2025-08-20T02:28:07ZengMDPI AGBiomolecules2218-273X2024-11-011411145010.3390/biom14111450Copy Number Variants in Cardiac Channelopathies: Still a Missed Part in Routine Arrhythmic DiagnosticsMaria Gnazzo0Giovanni Parlapiano1Francesca Di Lorenzo2Daniele Perrino3Silvia Genovese4Valentina Lanari5Daniela Righi6Federica Calì7Massimo Stefano Silvetti8Elena Falcone9Alessia Bauleo10Fabrizio Drago11Antonio Novelli12Anwar Baban13Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyCardiogenetic Center, Rare Diseases and Medical Genetics Units, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyCardiogenetic Center, Rare Diseases and Medical Genetics Units, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyLaboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyLaboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyLaboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyPediatric Cardiology and Arrhythmia/Syncope Complex Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyPediatric Cardiology and Arrhythmia/Syncope Complex Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyPediatric Cardiology and Arrhythmia/Syncope Complex Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyBiogenet, Medical and Forensic Genetics Laboratory, 87100 Cosenza, ItalyBiogenet, Medical and Forensic Genetics Laboratory, 87100 Cosenza, ItalyPediatric Cardiology and Arrhythmia/Syncope Complex Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyLaboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyCardiogenetic Center, Rare Diseases and Medical Genetics Units, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyInherited 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 <i>KCNQ1</i>, <i>KCNH2</i>, <i>SCN5A,</i> and <i>RYR2</i>. CNVs were reported in 119 patients from the literature and 21 from our cohort. Young patients with CNVs in <i>KCNQ1</i> show a Long QT (LQT) phenotype > 480 ms and a higher frequency of syncope. None of them had SCD. All patients with CNV in <i>KCNH2</i> had a positive phenotype for QT > 480 ms. CNVs in <i>SCN5A</i> were represented by the Brugada pattern, with major cardiac events mainly in males. Conversely, adult females show more supraventricular arrhythmias. <i>RYR2</i>-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.https://www.mdpi.com/2218-273X/14/11/1450channelopathiescopy number variantslong QTBrugadacatecholaminergic polymorphic ventricular tachycardia |
| spellingShingle | Maria Gnazzo Giovanni Parlapiano Francesca Di Lorenzo Daniele Perrino Silvia Genovese Valentina Lanari Daniela Righi Federica Calì Massimo Stefano Silvetti Elena Falcone Alessia Bauleo Fabrizio Drago Antonio Novelli Anwar Baban Copy Number Variants in Cardiac Channelopathies: Still a Missed Part in Routine Arrhythmic Diagnostics Biomolecules channelopathies copy number variants long QT Brugada catecholaminergic polymorphic ventricular tachycardia |
| title | Copy Number Variants in Cardiac Channelopathies: Still a Missed Part in Routine Arrhythmic Diagnostics |
| title_full | Copy Number Variants in Cardiac Channelopathies: Still a Missed Part in Routine Arrhythmic Diagnostics |
| title_fullStr | Copy Number Variants in Cardiac Channelopathies: Still a Missed Part in Routine Arrhythmic Diagnostics |
| title_full_unstemmed | Copy Number Variants in Cardiac Channelopathies: Still a Missed Part in Routine Arrhythmic Diagnostics |
| title_short | Copy Number Variants in Cardiac Channelopathies: Still a Missed Part in Routine Arrhythmic Diagnostics |
| title_sort | copy number variants in cardiac channelopathies still a missed part in routine arrhythmic diagnostics |
| topic | channelopathies copy number variants long QT Brugada catecholaminergic polymorphic ventricular tachycardia |
| url | https://www.mdpi.com/2218-273X/14/11/1450 |
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