{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T16:21:17Z","timestamp":1772900477962,"version":"3.50.1"},"reference-count":20,"publisher":"S. Karger AG","issue":"6","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiology"],"published-print":{"date-parts":[[2021]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Introduction:&lt;\/i&gt;&lt;\/b&gt; Brugada syndrome (BrS) is an inherited arrhythmia syndrome associated with an increased risk of sudden cardiac death. SCN5A is the most important disease-modifying gene for BrS, but many SCN5A variants have not been functionally characterized. Furthermore, the temperature dependency of SCN5A is only rarely explored in in vitro analyses. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; The clinical phenotype of the affected family was assessed by medical history, ECGs and ajmaline challenge. Whole-cell patch clamp recordings were performed on HEK 293T cells expressing Nav1.5-G1712S, a novel SCN5A variant found in the symptomatic family. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; Three male family members had experienced sudden cardiac death, sudden cardiac arrest, and rhythmogenic syncopes. Beside a positive ajmaline challenge with demarcation of a Brugada type 1 ECG, 1 patient also showed evidence of symptomatic cardiac conduction disease and sick sinus syndrome (SSS). In patch clamp analyses, Nav1.5-G1712S generated reduced peak currents as compared to the wild type. At body temperature, Nav1.5-G1712S additionally exhibited an enhanced slow inactivation and an impaired recovery from inactivation. &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; We conclude that G1712S is a pathogenic SCN5A loss-of function mutation at physiological temperature associated with an overlapping presentation of BrS, SSS, and cardiac conduction disease. <\/jats:p>","DOI":"10.1159\/000518210","type":"journal-article","created":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T21:01:08Z","timestamp":1625778068000},"page":"754-762","source":"Crossref","is-referenced-by-count":6,"title":["A Novel SCN5A Variant Causes Temperature-Sensitive Loss Of Function in a Family with Symptomatic Brugada Syndrome, Cardiac Conduction Disease, and Sick Sinus Syndrome"],"prefix":"10.1159","volume":"146","author":[{"given":"Karolina","family":"Sanner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Mueller-Leisse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christos","family":"Zormpas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Duncker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Leffler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Veltmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2021,7,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joa.2016.07.002"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.003379"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.035070"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12126"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1038\/srep07953"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2009.09.069"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.275.6.H2016"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.85.9.803"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-201X.2005.01496.x"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.109.853374"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2712"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.116.5.653"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctm.2016.05.001"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.22.10905"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2008.11.009"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.665406"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1253\/circj.68.473"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1046\/j.1540-8167.2001.00630.x"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.113.001340"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.08.043"}],"container-title":["Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/518210","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/518210","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:12:29Z","timestamp":1745421149000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000518210"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021]]},"references-count":20,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,12,1]]},"published-print":{"date-parts":[[2021,12,7]]}},"URL":"https:\/\/doi.org\/10.1159\/000518210","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.14931576","asserted-by":"subject"}]},"ISSN":["0008-6312","1421-9751"],"issn-type":[{"value":"0008-6312","type":"print"},{"value":"1421-9751","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021]]}}}