{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T19:52:35Z","timestamp":1779306755904,"version":"3.51.4"},"reference-count":11,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T00:00:00Z","timestamp":1709164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["VIDI\u201091718361"],"award-info":[{"award-number":["VIDI\u201091718361"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Genetic missense variants in\n                    <jats:italic>TNNI3K,<\/jats:italic>\n                    encoding troponin\u2010I interacting kinase, have been associated with dilated cardiomyopathy (DCM) and observed in families with supraventricular tachycardias (SVT). Previously, a family harboring the\n                    <jats:italic>TNNI3K<\/jats:italic>\n                    \u2010c.1615A\u2009&gt;\u2009G (p.Thr539Ala) variant presented with congenital junctional ectopic tachycardia (CJET), an arrhythmia that arises from the atrioventricular (AV) node and His bundle. However, this was a relatively small four\u2010generational family with limited genetic testing (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20093). We here describe a multigenerational family with CJET harboring a novel ultra\u2010rare\n                    <jats:italic>TNNI3K<\/jats:italic>\n                    variant:\n                    <jats:italic>TNNI3K<\/jats:italic>\n                    \u2010c.1729C\u2009&gt;\u2009T (p.Leu577Phe). Of all 18 variant carriers, 13 individuals presented with CJET, resulting in a genetic penetrance of 72%. In addition, CJET is reported in another small family harboring\n                    <jats:italic>TNNI3K<\/jats:italic>\n                    \u2010c.2225C\u2009&gt;\u2009T (p.Pro742Leu). Similar to the previously published CJET family, both\n                    <jats:italic>TNNI3K<\/jats:italic>\n                    variants demonstrate a substantial reduction of kinase activity. Our study contributes novel evidence supporting the involvement of\n                    <jats:italic>TNNI3K<\/jats:italic>\n                    genetic variants as significant contributors to CJET, shedding light on potential mechanisms underlying this cardiac arrhythmia.\n                  <\/jats:p>","DOI":"10.1111\/cge.14504","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:13:48Z","timestamp":1709252028000},"page":"37-46","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Reduced kinase function in two ultra\u2010rare\n                    <scp>\n                      <i>TNNI3K<\/i>\n                    <\/scp>\n                    variants in families with congenital junctional ectopic tachycardia"],"prefix":"10.1111","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8465-2978","authenticated-orcid":false,"given":"Caroline","family":"Pham","sequence":"first","affiliation":[{"name":"Department of Experimental Cardiology Heart Center Amsterdam UMC Location University of Amsterdam  Amsterdam The Netherlands"},{"name":"Amsterdam Cardiovascular Sciences Heart failure &amp; Arrhythmias  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7918-6634","authenticated-orcid":false,"given":"Tamara T.","family":"Koopmann","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Leiden University Medical Center  Leiden The Netherlands"},{"name":"Physiology and Experimental Medicine The Hospital for Sick Children &amp; Research Institute  Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9152-0295","authenticated-orcid":false,"given":"Jeffrey M.","family":"Vinocur","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4823-6974","authenticated-orcid":false,"given":"Nico A.","family":"Blom","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9252-0278","authenticated-orcid":false,"given":"Vivian","family":"Nogueira Silbiger","sequence":"additional","affiliation":[{"name":"Physiology and Experimental Medicine The Hospital for Sick Children &amp; Research Institute  Toronto Canada"},{"name":"Department of Clinical and Toxicological Analysis Federal University of Rio Grande do Norte  Natal Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirti","family":"Mittal","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine The Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1325-968X","authenticated-orcid":false,"given":"Marianne","family":"Bootsma","sequence":"additional","affiliation":[{"name":"Department of Cardiology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0816-8962","authenticated-orcid":false,"given":"Kaylin C. A.","family":"Palm","sequence":"additional","affiliation":[{"name":"Department of Experimental Cardiology Heart Center Amsterdam UMC Location University of Amsterdam  Amsterdam The Netherlands"},{"name":"Amsterdam Cardiovascular Sciences Heart failure &amp; Arrhythmias  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5276-1475","authenticated-orcid":false,"given":"Sally\u2010Ann B.","family":"Clur","sequence":"additional","affiliation":[{"name":"Department of Paediatric Cardiology, Emma Children's Hospital University Medical Center Amsterdam  Amsterdam The Netherlands"},{"name":"European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart \u2010 ERN GUARD\u2010Heart  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4461-4293","authenticated-orcid":false,"given":"Daniela Q. C. M.","family":"Barge\u2010Schaapveld","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5344-1278","authenticated-orcid":false,"given":"Robert M.","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Labatt Family Heart Centre, Department of Pediatrics, Hospital for Sick Children University of Toronto  Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6017-3796","authenticated-orcid":false,"given":"Elisabeth M.","family":"Lodder","sequence":"additional","affiliation":[{"name":"Department of Experimental Cardiology Heart Center Amsterdam UMC Location University of Amsterdam  Amsterdam The Netherlands"},{"name":"Amsterdam Cardiovascular Sciences Heart failure &amp; Arrhythmias  Amsterdam The Netherlands"},{"name":"Department of Human Genetics Amsterdam UMC location University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,2,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.122.003975"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2018.07.015"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu297"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2015.03.130"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/JOA3.12410"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/PNAS.93.8.3471"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102308\u20107"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/GIM.2015.30"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JACC.2004.11.053"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22126422"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14504","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T00:50:29Z","timestamp":1717375829000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14504"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,29]]},"references-count":11,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1111\/cge.14504"],"URL":"https:\/\/doi.org\/10.1111\/cge.14504","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14504\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14504\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14504\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14504\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14504\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14504\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,29]]},"assertion":[{"value":"2023-12-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}