{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T23:56:11Z","timestamp":1788825371457,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2014NextGenerationUE as part of PNRR MUR\u2014M4C2\u2014Investimento 1.3\u2014Public Call \u201cPartenariati Estesi\u201d\u2014D.D.","award":["341\/2022"],"award-info":[{"award-number":["341\/2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inherited arrhythmia syndromes include several different diseases, as well as Brugada syndrome (BrS), long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and short QT syndrome (SQTS). They represent, together with arrhythmogenic right ventricular dysplasia\/cardiomyopathy (ARVD\/C), an important cause of sudden cardiac death in the young. Most arrhythmia syndromes are inherited in an autosomal dominant manner, and genetic studies are suggested.: to report the spectrum of genetic variations and clinical phenotype in an Italian cohort with confirmed inherited arrhythmia syndromes and arrhythmogenic cardiomyopathy using whole-exome sequencing (WES). Patients with confirmed inherited arrhythmia syndromes and hereditary cardiomyopathy were recruited at the Cardiology Unit, University Polyclinic Hospital of Foggia, Italy and were included in this study. Genomic DNA samples were extracted from peripheral blood and conducted for WES. The variants were annotated using BaseSpace Variant Interpreter Annotation Engine 3.15.0.0 (Illumina). Reported variants were investigated using ClinVar, VarSome Franklin and a literature review. They were categorised agreeing to the criteria of the American College of Medical Genetics and Genomics. Overall, 62 patients were enrolled. Most of them had a clinical diagnosis of BrS (n 48, 77%). The remaining patients included in the present study had diagnosis of confirmed LQT (n 7, 11%), AR-DCM (n 4, 6.5%), ARVD (n 2, 3%), and SQT (n 1, 1.6%). Using the WES technique, 22 variants in 15 genes associated with Brugada syndrome were identified in 21 patients (34%). Among these, the SCN5A gene had the highest number of variants (6 variants, 27%), followed by KCNJ5 and CASQ2 (2 variants). Only one variant was identified in the remaining genes. In 27 patients with a clinical diagnosis of BrS, no gene variant was detected. In patients with confirmed LQT, SQT, 10 variants in 9 genes were identified. Among patients with ARVD and AR-DCM, 6 variants in 5 genes were found. Variants found in our cohort were classified as pathogenic (6), likely pathogenic (3), of uncertain significance (26), and benign (1). Two additional gene variants were classified as risk factors. In this study, 13 novel genetic variations were recognized to be associated with inherited arrhythmogenic cardiomyopathies. Our understanding of inherited arrhythmia syndromes continues to progress. The era of next-generation sequencing has advanced quickly, given new genetic evidence including pathogenicity, background genetic noise, and increased discovery of variants of uncertain significance. Although NGS study has some limits in finding the full genetic data of probands, large-scale gene sequencing can promptly be applied in real clinical practices, especially in inherited and possibly fatal arrhythmia syndromes.<\/jats:p>","DOI":"10.3390\/ijms26031200","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T05:40:46Z","timestamp":1738215646000},"page":"1200","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Genetic Background and Clinical Phenotype in an Italian Cohort with Inherited Arrhythmia Syndromes and Arrhythmogenic Cardiomyopathy (ACM): A Whole-Exome Sequencing Study"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9170-4668","authenticated-orcid":false,"given":"Maria","family":"d\u2019Apolito","sequence":"first","affiliation":[{"name":"Medical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9909-6513","authenticated-orcid":false,"given":"Francesco","family":"Santoro","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy"},{"name":"Cardiology Unit, University Polyclinic Hospital of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Ranaldi","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Cannito","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Santacroce","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9417-5909","authenticated-orcid":false,"given":"Ilaria","family":"Ragnatela","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Margaglione","sequence":"additional","affiliation":[{"name":"Cardiology Unit, University Polyclinic Hospital of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"D\u2019Andrea","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9610-7408","authenticated-orcid":false,"given":"Natale Daniele","family":"Brunetti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy"},{"name":"Cardiology Unit, University Polyclinic Hospital of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5627-9221","authenticated-orcid":false,"given":"Maurizio","family":"Margaglione","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Allegue, C., Coll, M., Mates, J., Campuzano, O., Iglesias, A., Sobrino, B., Brion, M., Amigo, J., Carracedo, A., and Brugada, P. 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