{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T04:45:50Z","timestamp":1766810750338,"version":"3.48.0"},"reference-count":28,"publisher":"Japanese Circulation Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Circ J"],"published-print":{"date-parts":[[2025,12,25]]},"DOI":"10.1253\/circj.cj-25-0447","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T22:08:42Z","timestamp":1760652522000},"page":"56-65","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of a Splice-Altering Variant in &lt;i&gt;SCN5A&lt;\/i&gt; Associated With Brugada Syndrome\u3000\u2015 Insights Into Splice Error Correction \u2015"],"prefix":"10.1253","volume":"90","author":[{"given":"Hideyuki","family":"Jinzai","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Shiga University of Medical Science"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Shiga University of Medical Science"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuichi","family":"Sawayama","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Shiga University of Medical Science"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeru","family":"Makiyama","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Kurosawa","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery Medicine, Kyoto University Graduate School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryotaro","family":"Kida","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Shiga University of Medical Science"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiko","family":"Ohno","sequence":"additional","affiliation":[{"name":"Medical Genome Center, National Cerebral and Cardiovascular Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihisa","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Shiga University of Medical Science"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiko","family":"Ajiro","sequence":"additional","affiliation":[{"name":"Division of Cancer RNA Research, National Cancer Center Research Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masatoshi","family":"Hagiwara","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery Medicine, Kyoto University Graduate School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minoru","family":"Horie","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Shiga University of Medical Science"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"330","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1. Krahn AD, Behr ER, Hamilton R, Probst V, Laksman Z, Han HC. Brugada syndrome. <i>J Am Coll Cardiol<\/i> 2022; 8: 386\u2013405.","DOI":"10.1016\/j.jacep.2021.12.001"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2. Kapplinger JD, Tester DJ, Alders M, Benito B, Berthet M, Brugada J, et al. An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. <i>Heart Rhythm<\/i> 2010; 7: 33\u201346, doi:10.1016\/j.hrthm.2009.09.069.","DOI":"10.1016\/j.hrthm.2009.09.069"},{"key":"3","doi-asserted-by":"publisher","unstructured":"3. Aiba T, Ohno S, Takegami M, Kato Y, Sakaguchi H, Shimamoto K, et al. Clinical impact of genetic testing for long QT syndrome: Evidence from a nationwide LQTS registry in Japan. <i>Circ J<\/i> 2025; 89: 835\u2013844, doi:10.1253\/circj.CJ-25-0105.","DOI":"10.1253\/circj.CJ-25-0105"},{"key":"4","doi-asserted-by":"publisher","unstructured":"4. O\u2019Neill MJ, Wada Y, Hall LD, Mitchell DW, Glazer AM, Roden DM. Functional assays reclassify suspected splice-altering variants of uncertain significance in Mendelian channelopathies. <i>Circ Genom Precis Med<\/i> 2022; 15: e003782, doi:10.1161\/CIRCGEN.122.003782.","DOI":"10.1161\/CIRCGEN.122.003782"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5. Shimada T, Ohkubo K, Abe K, Watanabe I, Makita N. A novel 5\u2032 splice site mutation of SCN5A associated with Brugada syndrome resulting in multiple cryptic transcripts. <i>Int J Cardiol<\/i> 2013; 158: 441\u2013443.","DOI":"10.1016\/j.ijcard.2012.04.114"},{"key":"6","doi-asserted-by":"publisher","unstructured":"6. Riepe TV, Khan M, Roosing S, Cremers FPM, \u2019t Hoen PAC. Benchmarking deep learning splice prediction tools using functional splice assays. <i>Hum Mutat<\/i> 2021; 42: 799\u2013810, doi:10.1002\/humu.24212.","DOI":"10.1002\/humu.24212"},{"key":"7","doi-asserted-by":"publisher","unstructured":"7. Nisson PE, Ally A, Watkins PC. Protocols for trapping internal and 3\u2032-terminal exons. <i>PCR Methods Appl<\/i> 1994; 4: s24\u2013s39, doi:10.1101\/gr.4.1.s24.","DOI":"10.1101\/gr.4.1.S24"},{"key":"8","doi-asserted-by":"publisher","unstructured":"8. Kato K, Ohno S, Sonoda K, Fukuyama M, Makiyama T, Ozawa T, et al. LMNA missense mutation causes nonsense-mediated mRNA decay and severe dilated cardiomyopathy. <i>Circ Genom Precis Med<\/i> 2020; 13: 435\u2013443, doi:10.1161\/CIRCGEN.119.002853.","DOI":"10.1161\/CIRCGEN.119.002853"},{"key":"9","doi-asserted-by":"publisher","unstructured":"9. Wuriyanghai Y, Makiyama T, Sasaki K, Kamakura T, Yamamoto Y, Hayano M, et al. Complex aberrant splicing in the induced pluripotent stem cell-derived cardiomyocytes from a patient with long QT syndrome carrying KCNQ1-A344Aspl mutation. <i>Heart Rhythm<\/i> 2018; 15: 1566\u20131574, doi:10.1016\/j.hrthm.2018.05.028.","DOI":"10.1016\/j.hrthm.2018.05.028"},{"key":"10","doi-asserted-by":"publisher","unstructured":"10. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. <i>Genet Med<\/i> 2015; 17: 405\u2013424, doi:10.1038\/gim.2015.30.","DOI":"10.1038\/gim.2015.30"},{"key":"11","doi-asserted-by":"publisher","unstructured":"11. Jaganathan K, Kyriazopoulou Panagiotopoulou S, McRae JF, Darbandi SF, Knowles D, Li YI, et al. Predicting splicing from primary sequence with deep learning. <i>Cell<\/i> 2019; 176: 535\u2013548.e24, doi:10.1016\/j.cell.2018.12.015.","DOI":"10.1016\/j.cell.2018.12.015"},{"key":"12","doi-asserted-by":"publisher","unstructured":"12. Fuse N, Sakurai-Yageta M, Katsuoka F, Danjoh I, Shimizu R, Tamiya G, et al. Establishment of integrated biobank for precision medicine and personalized healthcare: The Tohoku Medical Megabank Project. <i>JMA J<\/i> 2019; 2: 113\u2013122, doi:10.31662\/jmaj.2019-0014.","DOI":"10.31662\/jmaj.2019-0014"},{"key":"13","doi-asserted-by":"publisher","unstructured":"13. Kuriyama S, Yaegashi N, Nagami F, Arai T, Kawaguchi Y, Osumi N, et al. The Tohoku Medical Megabank Project: Design and mission. <i>J Epidemiol<\/i> 2016; 26: 493\u2013511, doi:10.2188\/jea.JE20150268.","DOI":"10.2188\/jea.JE20150268"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. <i>Cell<\/i> 2007; 131: 861\u2013872, doi:10.1016\/j.cell.2007.11.019.","DOI":"10.1016\/j.cell.2007.11.019"},{"key":"15","doi-asserted-by":"publisher","unstructured":"15. Yang L, Soonpaa MH, Adler ED, Roepke TK, Kattman SJ, Kennedy M, et al. Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population. <i>Nature<\/i> 2008; 453: 524\u2013528, doi:10.1038\/nature06894.","DOI":"10.1038\/nature06894"},{"key":"16","doi-asserted-by":"publisher","unstructured":"16. Soemedi R, Cygan KJ, Rhine CL, Wang J, Bulacan C, Yang J, et al. Pathogenic variants that alter protein code often disrupt splicing. <i>Nat Genet<\/i> 2017; 49: 848\u2013855, doi:10.1038\/ng.3837.","DOI":"10.1038\/ng.3837"},{"key":"17","doi-asserted-by":"publisher","unstructured":"17. Krawczak M, Reiss J, Cooper DN. The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: Causes and consequences. <i>Hum Genet<\/i> 1992; 90: 41\u201354, doi:10.1007\/BF00210743.","DOI":"10.1007\/BF00210743"},{"key":"18","doi-asserted-by":"publisher","unstructured":"18. Singer ES, Crowe J, Holliday M, Isbister JC, Lal S, Nowak N, et al. The burden of splice-disrupting variants in inherited heart disease and unexplained sudden cardiac death. <i>NPJ Genom Med<\/i> 2023; 8: 29, doi:10.1038\/s41525-023-00373-w.","DOI":"10.1038\/s41525-023-00373-w"},{"key":"19","doi-asserted-by":"publisher","unstructured":"19. Yeo G, Burge CB. Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals. <i>J Comput Biol<\/i> 2004; 11: 377\u2013394, doi:10.1089\/1066527041410418.","DOI":"10.1089\/1066527041410418"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20. Reese MG, Eeckman FH, Kulp D, Haussler D. Improved splice site detection in Genie. <i>J Comput Biol<\/i> 1997; 4: 311\u2013323.","DOI":"10.1089\/cmb.1997.4.311"},{"key":"21","doi-asserted-by":"publisher","unstructured":"21. Kurosawa R, Iida K, Ajiro M, Awaya T, Yamada M, Kosaki K, et al. PDIVAS: Pathogenicity predictor for deep-intronic variants causing aberrant splicing. <i>BMC Genomics<\/i> 2023; 24: 601, doi:10.1186\/s12864-023-09645-2.","DOI":"10.1186\/s12864-023-09645-2"},{"key":"22","doi-asserted-by":"publisher","unstructured":"22. Heo WY, Jang SY, Park TK, Ki CS, Kim JW, Kim DK, et al. Identification of two novel COL3A1 variants in patients with vascular Ehlers-Danlos syndrome. <i>Mol Genet Genomic Med<\/i> 2023; 11: e2240, doi:10.1002\/mgg3.2240.","DOI":"10.1002\/mgg3.2240"},{"key":"23","doi-asserted-by":"publisher","unstructured":"23. Rodr\u00edguez-Hidalgo M, de Bruijn SE, Corradi Z, Rodenburg K, Lara-L\u00f3pez A, Valverde-Meg\u00edas A, et al. ABCA4 c.6480-35A&gt;G, a novel branchpoint variant associated with Stargardt disease. <i>Front Genet<\/i> 2023; 14: 1234032, doi:10.3389\/fgene.2023.1234032.","DOI":"10.3389\/fgene.2023.1234032"},{"key":"24","doi-asserted-by":"publisher","unstructured":"24. Mazin PV, Khaitovich P, Cardoso-Moreira M, Kaessmann H. Alternative splicing during mammalian organ development. <i>Nat Genet<\/i> 2021; 53: 925\u2013934, doi:10.1038\/s41588-021-00851-w.","DOI":"10.1038\/s41588-021-00851-w"},{"key":"25","doi-asserted-by":"publisher","unstructured":"25. de Smet MD, Meenken CJ, van den Horn GJ. Fomivirsen: A phosphorothioate oligonucleotide for the treatment of CMV retinitis. <i>Ocul Immunol Inflamm<\/i> 1999; 7: 189\u2013198, doi:10.1076\/ocii.7.3.189.4007.","DOI":"10.1076\/ocii.7.3.189.4007"},{"key":"26","doi-asserted-by":"publisher","unstructured":"26. Visser ME, Wagener G, Baker BF, Geary RS, Donovan JM, Beuers UH, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: A randomized, double-blind, placebo-controlled trial. <i>Eur Heart J<\/i> 2012; 33: 1142\u20131149, doi:10.1093\/eurheartj\/ehs023.","DOI":"10.1093\/eurheartj\/ehs023"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27. Chiriboga CA, Swoboda KJ, Darras BT, Iannaccone ST, Montes J, De Vivo DC, et al. Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy. <i>Neurology<\/i> 2016; 86: 890\u2013897.","DOI":"10.1212\/WNL.0000000000002445"},{"key":"28","doi-asserted-by":"publisher","unstructured":"28. Ishikawa T, Kimoto H, Mishima H, Yamagata K, Ogata S, Aizawa Y, et al. Functionally validated SCN5A variants allow interpretation of pathogenicity and prediction of lethal events in Brugada syndrome. <i>Eur Heart J<\/i> 2021; 42: 2854\u20132863, doi:10.1093\/eurheartj\/ehab254.","DOI":"10.1093\/eurheartj\/ehab254"}],"container-title":["Circulation Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/circj\/90\/1\/90_CJ-25-0447\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T03:18:05Z","timestamp":1766805485000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/circj\/90\/1\/90_CJ-25-0447\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,25]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.1253\/circj.cj-25-0447","relation":{},"ISSN":["1346-9843","1347-4820"],"issn-type":[{"type":"print","value":"1346-9843"},{"type":"electronic","value":"1347-4820"}],"subject":[],"published":{"date-parts":[[2025,12,25]]},"article-number":"CJ-25-0447"}}