{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:46:13Z","timestamp":1789145173540,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,9,5]],"date-time":"2016-09-05T00:00:00Z","timestamp":1473033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"crossref","award":["2015YGYL008"],"award-info":[{"award-number":["2015YGYL008"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Science Fund for Fostering Talents in Basic Research of China","award":["J1103514"],"award-info":[{"award-number":["J1103514"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:p>Congenital heart disease (CHD), one of the causes of childhood morbidity and mortality, is mainly triggered by a combination of environmental and genetic factors. Several susceptible genes, such as <jats:italic>NKX2\u20105<\/jats:italic>, <jats:italic>GATA4<\/jats:italic> and <jats:italic>TBX5<\/jats:italic>, have been reported as closely related to heart and vessel development. CHD subtypes are classified into diverse clinical phenotypes, such as atrial septal defects (ASD), ventricular septal defects (VSD), tetralogy of Fallot (TOF), and Holt\u2013Oram syndrome (HOS). Here, we summarize the associations of the genetic variants in these three genes with CHD subtypes. CHD\u2010associated variants of <jats:italic>NKX2\u20105<\/jats:italic> locate mainly in the tinman domain and the homeodomain. Mutations in the homeodomain are correlated with ASD and atrioventricular (AV) block subtypes. VSD\u2010associated variants of <jats:italic>GATA4<\/jats:italic> are mainly at its terminal ends. Variants of <jats:italic>TBX5<\/jats:italic> gene are primarily in exons 3, 4, 5 and 7 and highly associated with HOS subtype. Hence, the variant distribution of <jats:italic>NKX2\u20105<\/jats:italic>, <jats:italic>GATA4<\/jats:italic> and <jats:italic>TBX5<\/jats:italic> are tightly associated with particular CHD subtypes. Further structure\u2010modelling analysis revealed that these mutated amino acid residuals maintain their DNA\u2010binding ability and structural stability. Therefore structural features of these genes may be used to predict the high risk of CHD subtypes in infants.<\/jats:p>","DOI":"10.1111\/cge.12835","type":"journal-article","created":{"date-parts":[[2016,7,18]],"date-time":"2016-07-18T10:22:42Z","timestamp":1468837362000},"page":"349-354","source":"Crossref","is-referenced-by-count":46,"title":["Congenital heart diseases and their association with the variant distribution features on susceptibility genes"],"prefix":"10.1111","volume":"91","author":[{"given":"W.","family":"Su","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan 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