{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:04:25Z","timestamp":1792670665491,"version":"4.5.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,12,13]],"date-time":"2017-12-13T00:00:00Z","timestamp":1513123200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,12,13]],"date-time":"2017-12-13T00:00:00Z","timestamp":1513123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dilated cardiomyopathy (DCM) is a primary cause of heart failure, life-threatening arrhythmias, and cardiac death. Pathogenic mutations have been identified at the loci of more than 50 genes in approximately 50% of DCM cases, while the etiologies of the remainder have yet to be determined. In this study, we applied whole exome sequencing in combination with segregation analysis to one pedigree with familial DCM, and identified a read-through mutation (c.2459\u2009A\u2009&gt;\u2009C; p.*820Sext*19) in the myosin light chain kinase 3 gene (<jats:italic>MYLK3<\/jats:italic>). We then conducted <jats:italic>MYLK3<\/jats:italic> gene screening of 15 DCM patients (7 familial and 8 sporadic) who were negative for mutation screening of the previously-reported cardiomyopathy-causing genes, and identified another case with a <jats:italic>MYLK3<\/jats:italic> frameshift mutation (c.1879_1885del; p.L627fs*41). <jats:italic>In vitro<\/jats:italic> experiments and immunohistochemistry suggested that the <jats:italic>MYLK3<\/jats:italic> mutations identified in this study result in markedly reduced levels of protein expression and myosin light chain 2 phosphorylation. This is the first report that <jats:italic>MYLK3<\/jats:italic> mutations can cause DCM in humans. The clinical phenotypes of DCM patients were consistent with <jats:italic>MYLK3<\/jats:italic> loss-of-function mouse and zebrafish models in which cardiac enlargement and heart failure are observed. Our findings highlight an essential role for cardiac myosin light chain kinase in the human heart.<\/jats:p>","DOI":"10.1038\/s41598-017-17769-1","type":"journal-article","created":{"date-parts":[[2017,12,7]],"date-time":"2017-12-07T10:42:05Z","timestamp":1512643325000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Identification of MYLK3 mutations in familial dilated cardiomyopathy"],"prefix":"10.1038","volume":"7","author":[{"given":"Takashige","family":"Tobita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seitaro","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Morita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruhiro","family":"Toko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenta","family":"Uto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhisa","family":"Hagiwara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0438-1544","authenticated-orcid":false,"given":"Hiroyuki","family":"Aburatani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issei","family":"Komuro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,12,13]]},"reference":[{"key":"17769_CR1","doi-asserted-by":"publisher","first-page":"e240","DOI":"10.1161\/CIR.0b013e31829e8807","volume":"128","author":"CW Yancy","year":"2013","unstructured":"Yancy, C. 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