Till Joscha Demal, Melina Heise, Benedikt Reiz, Deepika Dogra, Ingrid Braenne, Hermann Reichenspurner, Jörg Männer, Zouhair Aherrahrou, Heribert Schunkert, Jeanette Erdmann, Salim Abdelilah-Seyfried
- The genetics of many congenital heart diseases (CHDs) can only unsatisfactorily be explained by known chromosomal or Mendelian syndromes. Here, we present sequencing data of a family with a potentially multigenic origin of CHD. Twelve of nineteen family members carry a familial mutation [NM_004329.2:c.1328 G > A (p.R443H)] which encodes a predicted deleterious variant of BMPR1A. This mutation co-segregates with a linkage region on chromosome 1 that associates with the emergence of severe CHDs including Ebstein’s anomaly, atrioventricular septal defect, and others. We show that the continuous overexpression of the zebrafish homologous mutation bmpr1aap.R438H within endocardium causes a reduced AV valve area, a downregulation of Wnt/ß-catenin signalling at the AV canal, and growth of additional tissue mass in adult zebrafish hearts. This finding opens the possibility of testing genetic interactions between BMPR1A and other candidate genes within linkage region 1 which may provide a first step towards unravelling more complex geneticThe genetics of many congenital heart diseases (CHDs) can only unsatisfactorily be explained by known chromosomal or Mendelian syndromes. Here, we present sequencing data of a family with a potentially multigenic origin of CHD. Twelve of nineteen family members carry a familial mutation [NM_004329.2:c.1328 G > A (p.R443H)] which encodes a predicted deleterious variant of BMPR1A. This mutation co-segregates with a linkage region on chromosome 1 that associates with the emergence of severe CHDs including Ebstein’s anomaly, atrioventricular septal defect, and others. We show that the continuous overexpression of the zebrafish homologous mutation bmpr1aap.R438H within endocardium causes a reduced AV valve area, a downregulation of Wnt/ß-catenin signalling at the AV canal, and growth of additional tissue mass in adult zebrafish hearts. This finding opens the possibility of testing genetic interactions between BMPR1A and other candidate genes within linkage region 1 which may provide a first step towards unravelling more complex genetic patterns in cardiovascular disease aetiology.…
MetadatenAuthor details: | Till Joscha DemalGND, Melina HeiseGND, Benedikt ReizORCiD, Deepika DograGND, Ingrid Braenne, Hermann ReichenspurnerGND, Jörg Männer, Zouhair AherrahrouGND, Heribert SchunkertGND, Jeanette ErdmannORCiDGND, Salim Abdelilah-SeyfriedORCiDGND |
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DOI: | https://doi.org/10.1038/s41598-019-39648-7 |
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ISSN: | 2045-2322 |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/30814609 |
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Title of parent work (English): | Scientific reports |
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Publisher: | Nature Publ. Group |
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Place of publishing: | London |
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Publication type: | Article |
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Language: | English |
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Date of first publication: | 2019/02/27 |
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Publication year: | 2019 |
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Release date: | 2021/04/06 |
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Volume: | 9 |
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Number of pages: | 12 |
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Funding institution: | Excellence cluster REBIRTH [SFB958]; DZHK (Deutsches Zentrum fur Herz-Kreislauf-Forschung e.V.); Kaltenbach grant of the Deutsche Herzstiftung e.V.; scholarship "Lubecker Exzellenzmedizin" of the University of Lubeck; DZHK; Joachim Herz foundation; Deutsche Forschungsgemeinschaft (DFG)German Research Foundation (DFG) [SE2016/7-2, SE2016/10-1] |
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Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
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DDC classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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Peer review: | Referiert |
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Publishing method: | Open Access / Gold Open-Access |
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| DOAJ gelistet |
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License (German): | CC-BY - Namensnennung 4.0 International |
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