{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T07:23:03Z","timestamp":1784618583011,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,8,5]],"date-time":"2014-08-05T00:00:00Z","timestamp":1407196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec><jats:label\/><jats:p>Atrial septal defect (ASD) is the most common congenital heart defect clinically characterized by an opening in the atrial septum. Mutations in <jats:italic>GATA4<\/jats:italic>, <jats:italic>TBX5<\/jats:italic>, and <jats:italic>NKX2\u20105<\/jats:italic> underlie this phenotype. Here, we report on the identification of a novel \u20106 G\u2009&gt;\u2009C mutation in the highly conserved Kozak sequence in the 5'UTR of <jats:italic>GATA4<\/jats:italic> in a small family presenting with two different forms of ASD. This is the first time a mutation in the Kozak sequence has been linked to heart disease. Functional assays demonstrate reduced GATA4 translation, though the GATA4 transcript levels remain normal. This leads to a reduction of GATA4 protein level, consequently diminishing the ability of GATA4 to transactivate target genes, as demonstrated by using the GATA4\u2010driven <jats:italic>Nppa<\/jats:italic> (ANF) promoter. In conclusion, we identified a mutation in the <jats:italic>GATA4<\/jats:italic> Kozak sequence that likely contributes to the pathogenesis of ASD. In general, it points to the importance of accurate protein level regulation during heart development and emphasizes the need to analyze the entire transcribed region when screening for mutations. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36703","type":"journal-article","created":{"date-parts":[[2014,8,5]],"date-time":"2014-08-05T18:03:29Z","timestamp":1407261809000},"page":"2732-2738","source":"Crossref","is-referenced-by-count":27,"title":["A mutation in the Kozak sequence of <i>GATA4<\/i> hampers translation in a family with atrial septal defects"],"prefix":"10.1002","volume":"164","author":[{"given":"Rajiv A.","family":"Mohan","sequence":"first","affiliation":[{"name":"Department of Anatomy Embryology &amp; Physiology Academic Medical Center Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaartje","family":"van Engelen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Academic Medical Center Amsterdam the Netherlands"},{"name":"Department of Cardiology Academic Medical Center Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Stefanovic","sequence":"additional","affiliation":[{"name":"Department of Anatomy Embryology &amp; 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