{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T03:24:35Z","timestamp":1773804275967,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T00:00:00Z","timestamp":1692576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Onassis Foundation","award":["505"],"award-info":[{"award-number":["505"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Congenital heart malformations (CHMs) make up between 2 and 3% of annual human births. Bone morphogenetic proteins (BMPs) signalling is required for chamber myocardium development. We examined for possible molecular defects in the bone morphogenetic protein 2 and 4 (BMP2, -4) genes by sequencing analysis of all coding exons, as well as possible transcription or protein expression deregulation by real-time PCR and ELISA, respectively, in 52 heart biopsies with congenital malformations (atrial septal defect (ASD), ventricular septal defect (VSD), tetralogy ofFallot (ToF) and complex cases) compared to 10 non-congenital heart disease (CHD) hearts. No loss of function mutations was found; only synonymous single nucleotide polymorphisms (SNPs) in the BMP2 and BMP4 genes were found. Deregulation of the mRNA expression and co-expression profile of the two genes (BMP2\/BMP4) was observed in the affected compared to the normal hearts. BMP2 and -4 protein expression levels were similar in normal and affected hearts. This is the first study assessing the role of BMP-2 and 4 in congenital heart malformations. Our analysis did not reveal molecular defects in the BMP2 and -4 genes that could support a causal relationship with the congenital defects present in our patients. Importantly, sustained mRNA and protein expression of BMP2 and -4 in CHD cases compared to controls indicates possible temporal epigenetic, microRNA or post-transcriptional regulation mechanisms governing the initial stages of cardiac malformation.<\/jats:p>","DOI":"10.3390\/diagnostics13162717","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T08:53:31Z","timestamp":1692608011000},"page":"2717","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Investigation of the Role of BMP2 and -4 in ASD, VSD and Complex Congenital Heart Disease"],"prefix":"10.3390","volume":"13","author":[{"given":"Dimitrios","family":"Bobos","sequence":"first","affiliation":[{"name":"Department of Pediatric Cardiothoracic Surgery, Onassis Cardiac Surgery Center, 17674 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giannoula","family":"Soufla","sequence":"additional","affiliation":[{"name":"Department of Hematology and Blood Transfusion, Onassis Cardiac Surgery Center, 17674 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitrios C.","family":"Angouras","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Faculty of Medicine, Attikon University Hospital, National Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Lekakis","sequence":"additional","affiliation":[{"name":"Second Department of Cardiology, Attikon Hospital, Athens Medical School, National Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sotirios","family":"Georgopoulos","sequence":"additional","affiliation":[{"name":"First Department of Surgery, Laikon General Hospital, Medical School, National Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Euthemia","family":"Melissari","sequence":"additional","affiliation":[{"name":"Department of Hematology and Blood Transfusion, Onassis Cardiac Surgery Center, 17674 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1016\/S0735-1097(02)01886-7","article-title":"The incidence of congenital heart disease","volume":"39","author":"Hoffman","year":"2002","journal-title":"J. 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