{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T22:19:20Z","timestamp":1785449960269,"version":"3.56.0"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,2,19]],"date-time":"2019-02-19T00:00:00Z","timestamp":1550534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007162","name":"Guangdong Science and Technology Department","doi-asserted-by":"publisher","award":["2013B030400001"],"award-info":[{"award-number":["2013B030400001"]}],"id":[{"id":"10.13039\/501100007162","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007162","name":"Guangdong Science and Technology Department","doi-asserted-by":"publisher","award":["2014A050503048"],"award-info":[{"award-number":["2014A050503048"]}],"id":[{"id":"10.13039\/501100007162","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007162","name":"Guangdong Science and Technology Department","doi-asserted-by":"publisher","award":["2017A070701013"],"award-info":[{"award-number":["2017A070701013"]}],"id":[{"id":"10.13039\/501100007162","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Cardiac septal defects account for more than 50% of congenital heart defects. Ankyrin repeat domain 1 (<jats:italic>ANKRD1<\/jats:italic>) is an important transcription factor that is mutated in multiple cardiac diseases; however, a relationship between the <jats:italic>ANKRD1<\/jats:italic> mutation and cardiac septal defects has not been described.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We examined genetic mutations in a large family with three cardiac septal defect patients. Whole exome sequencing, bioinformatics and conservation analysis were utilized to predict the pathogenicity of candidate mutations. Dual luciferase reporter assay and nuclear localization experiments were performed to evaluate the influence of target mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A heterozygous, missense variant of <jats:italic>ANKRD1<\/jats:italic> (MIM* 609599): NM_014391: exon6: c.C560T:p.S187F was identified at a highly conserved region. Sanger sequencing in extended family members demonstrated an incomplete inheritance model. When co\u2010activated with NKX2.5, <jats:italic>ANKRD1<\/jats:italic> repressed ANF expression as assessed by a dual\u2010luciferase reporter assay, and p.S187F mutation enhanced the repressive effect (0.318\u00a0\u00b1\u00a00.018 versus 0.564\u00a0\u00b1\u00a00.048, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.01). A real\u2010time polymerase chain reaction confirmed that p.S187F mutation of <jats:italic>ANKRD1<\/jats:italic> decreased the expression of endogenous <jats:italic>ANF<\/jats:italic> (0.85\u00a0\u00b1\u00a00.05 versus 0.61\u00a0\u00b1\u00a00.04, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.01). Furthermore, nuclear localization experiments demonstrated that the mutation significantly decreased the nuclear distribution of <jats:italic>ANKRD1<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present study is the first to identify the p.S187F mutant of <jats:italic>ANKRD1<\/jats:italic>, which is associated with cardiac septal defects.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3070","type":"journal-article","created":{"date-parts":[[2019,1,19]],"date-time":"2019-01-19T18:48:40Z","timestamp":1547923720000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Ankyrin repeat domain 1: A novel gene for cardiac septal defects"],"prefix":"10.1002","volume":"21","author":[{"given":"Yongchao","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Cardiac Surgery Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"},{"name":"Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"},{"name":"Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueheng","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shufang","family":"Huang","sequence":"additional","affiliation":[{"name":"Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"},{"name":"Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"},{"name":"Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences  Guangzhou Guangdong 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