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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2015,10,6]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Cardiovascular disease remains the leading cause of mortality in the United States, and cardiac arrhythmia underlies the majority of these deaths. Here, we report a new mechanism for congenital human cardiac arrhythmia due to defects in the regulation of the primary cardiac Na\n                    <jats:sub>v<\/jats:sub>\n                    channel, Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5 (\n                    <jats:italic>SCN5A<\/jats:italic>\n                    ), by a family of signaling molecules termed fibroblast growth factor homologous factors (FHFs). Individuals harboring\n                    <jats:italic>SCN5A<\/jats:italic>\n                    variants that affect Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5\/FHF interactions display atrial and ventricular phenotypes, syncope, and sudden cardiac death. The human variant results in aberrant Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5 inactivation, causing prolonged action potential duration and afterdepolarizations in murine myocytes, thereby providing a rationale for the human arrhythmia.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1516430112","type":"journal-article","created":{"date-parts":[[2015,9,21]],"date-time":"2015-09-21T23:08:42Z","timestamp":1442876922000},"page":"12528-12533","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":63,"title":["<i>SCN5A<\/i>\n                    variant that blocks fibroblast growth factor homologous factor regulation causes human arrhythmia"],"prefix":"10.1073","volume":"112","author":[{"given":"Hassan","family":"Musa","sequence":"first","affiliation":[{"name":"Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"},{"name":"Department of Physiology &amp; Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal F.","family":"Kline","sequence":"additional","affiliation":[{"name":"Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"},{"name":"Department of Physiology &amp; Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy C.","family":"Sturm","sequence":"additional","affiliation":[{"name":"Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"},{"name":"Department of Internal Medicine, Division of Human Genetics, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel","family":"Murphy","sequence":"additional","affiliation":[{"name":"Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"},{"name":"Department of Physiology &amp; Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Adelman","sequence":"additional","affiliation":[{"name":"Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"},{"name":"Department of Physiology &amp; Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaojian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine and Ion Channel Research Unit, Duke University Medical Center, Durham, NC 27709;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haidun","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Medicine and Ion Channel Research Unit, Duke University Medical Center, Durham, NC 27709;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin L.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"},{"name":"Department of Physiology &amp; Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Csepe","sequence":"additional","affiliation":[{"name":"Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"},{"name":"Department of Physiology &amp; Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"Kilic","sequence":"additional","affiliation":[{"name":"Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"},{"name":"Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S. D.","family":"Higgins","sequence":"additional","affiliation":[{"name":"Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"},{"name":"Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M. L.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"},{"name":"Department of Physiology &amp; Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"},{"name":"Department of Internal Medicine, Division of Cardiovascular Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim V.","family":"Fedorov","sequence":"additional","affiliation":[{"name":"Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"},{"name":"Department of Physiology &amp; Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Weiss","sequence":"additional","affiliation":[{"name":"Dorothy M. 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