{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:12:33Z","timestamp":1791616353258,"version":"4.3.4"},"reference-count":147,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2013,8,30]],"date-time":"2013-08-30T00:00:00Z","timestamp":1377820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:p>\n                    <jats:bold>Abstract\u2002<\/jats:bold>\n                    Over the last two decades, an increasing number of\n                    <jats:italic>SCN5A<\/jats:italic>\n                    mutations have been described in patients with long QT syndrome type 3 (LQT3), Brugada syndrome, (progressive) conduction disease, sick sinus syndrome, atrial standstill, atrial fibrillation, dilated cardiomyopathy, and sudden infant death syndrome (SIDS). Combined genetic, electrophysiological and molecular studies have provided insight into the dysfunction and dysregulation of the cardiac sodium channel in the setting of\n                    <jats:italic>SCN5A<\/jats:italic>\n                    mutations identified in patients with these inherited arrhythmia syndromes. However, risk stratification and patient management is hindered by the reduced penetrance and variable disease expressivity in sodium channelopathies. Furthermore, various\n                    <jats:italic>SCN5A<\/jats:italic>\n                    \u2010related arrhythmia syndromes are known to display mixed phenotypes known as cardiac sodium channel overlap syndromes. Determinants of variable disease expressivity, including genetic background and environmental factors, are suspected but still largely unknown. Moreover, it has become increasingly clear that sodium channel function and regulation is more complicated than previously assumed, and the sodium channel may play additional, as of yet unrecognized, roles in cardiac structure and function. Development of cardiac structural abnormalities secondary to\n                    <jats:italic>SCN5A<\/jats:italic>\n                    mutations has been reported, but the clinical relevance and underlying mechanisms are unclear. Increased insight into these issues would enable a major next step in research related to cardiac sodium channel disease, ultimately enabling improved diagnosis, risk stratification and treatment strategies.\n                  <\/jats:p>","DOI":"10.1113\/jphysiol.2013.256461","type":"journal-article","created":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T20:58:35Z","timestamp":1372712315000},"page":"4099-4116","source":"Crossref","is-referenced-by-count":182,"title":["Cardiac sodium channelopathy associated with\n                    <i>SCN5A<\/i>\n                    mutations: electrophysiological, molecular and genetic aspects"],"prefix":"10.1113","volume":"591","author":[{"given":"Carol 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