{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:35:15Z","timestamp":1787960115119,"version":"build-2784847793"},"reference-count":13,"publisher":"Cambridge University Press (CUP)","issue":"3","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Cardiol Young"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec id=\"S1047951123003219_as1\"><jats:title>Introduction:<\/jats:title><jats:p>The NKX2.5 gene is an important cardiac developmental transcription factor, and variants in this gene are most commonly associated with CHD. However, there is an increased need to recognise associations with conduction disease and potentially dangerous ventricular arrhythmias. There is an increased risk of arrhythmia and sudden cardiac death in patients with NKX2.5 variants, an association with relatively less attention in the literature.<\/jats:p><\/jats:sec><jats:sec id=\"S1047951123003219_as2\"><jats:title>Methods:<\/jats:title><jats:p>We created a family pedigree and reconstructed familial relationships involving numerous relatives with CHD, conduction disease, and ventricular non-compaction following the sudden death of one family member. Two informative but distantly related family members had genetic testing to determine the cause of arrhythmias via arrhythmia\/cardiomyopathy gene testing, and we identified obligate genetic-positive relatives based on family relationships and Mendelian inheritance pattern.<\/jats:p><\/jats:sec><jats:sec id=\"S1047951123003219_as3\"><jats:title>Results:<\/jats:title><jats:p>We identified a novel pathogenic variant in the NKX2.5 gene (c.437C &gt; A; p. Ser146*), and segregation analysis allowed us to link family cardiac phenotypes including CHD, conduction disease, left ventricular non-compaction, and ventricular arrhythmias\/sudden cardiac death.<\/jats:p><\/jats:sec><jats:sec id=\"S1047951123003219_as4\"><jats:title>Conclusions:<\/jats:title><jats:p>We report a novel NKX2.5 gene variant linking a spectrum of familial heart disease, and we also encourage recognition of the association between NKX2.5 gene and potentially dangerous ventricular arrhythmias, which will inform clinical risk stratification, screening, and management.<\/jats:p><\/jats:sec>","DOI":"10.1017\/s1047951123003219","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T06:12:42Z","timestamp":1694499162000},"page":"654-658","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":3,"title":["Novel <i>NKX2.5<\/i> variant associated with congenital heart disease and increased risk of malignant arrhythmia and sudden cardiac death"],"prefix":"10.1017","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5597-0202","authenticated-orcid":false,"given":"Benjamin M.","family":"Helm","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Baud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Shopp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3966-4261","authenticated-orcid":false,"given":"Adam C.","family":"Kean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D.","family":"Ayers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2023,9,12]]},"reference":[{"key":"S1047951123003219_ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrcr.2018.08.001"},{"key":"S1047951123003219_ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2011.05.020"},{"key":"S1047951123003219_ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2012.07.033"},{"key":"S1047951123003219_ref4","doi-asserted-by":"publisher","DOI":"10.1111\/chd.12317"},{"key":"S1047951123003219_ref3","first-page":"103797","article-title":"An adult female with 5q34-q35.2 deletion: a rare syndromic presentation of left ventricular non-compaction and congenital heart disease. Eur","volume":"63","author":"Arya","year":"2020","journal-title":"J Med Genet"},{"key":"S1047951123003219_ref1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8154"},{"key":"S1047951123003219_ref6","first-page":"691203","article-title":"Case report: a novel NKX2-5 mutation in a family with congenital heart defects, left ventricular non-compaction, conduction disease, and sudden cardiac death. Front","volume":"8","author":"Morlanes-Gracia","year":"2021","journal-title":"Cardiovasc Med"},{"key":"S1047951123003219_ref5","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-014-0917-3"},{"key":"S1047951123003219_ref8","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euu194"},{"key":"S1047951123003219_ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.05.015"},{"key":"S1047951123003219_ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2014.08.003"},{"key":"S1047951123003219_ref13","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.117.001735"},{"key":"S1047951123003219_ref10","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehn219"}],"container-title":["Cardiology in the Young"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S1047951123003219","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T10:58:34Z","timestamp":1709895514000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S1047951123003219\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,12]]},"references-count":13,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["S1047951123003219"],"URL":"https:\/\/doi.org\/10.1017\/s1047951123003219","relation":{},"ISSN":["1047-9511","1467-1107"],"issn-type":[{"value":"1047-9511","type":"print"},{"value":"1467-1107","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,12]]},"assertion":[{"value":"\u00a9 The Author(s), 2023. Published by Cambridge University Press","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}}]}}