{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:59:15Z","timestamp":1791917955326,"version":"4.3.4"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002996","name":"Dutch Heart Foundation","doi-asserted-by":"crossref","award":["2013\u00a0T042"],"award-info":[{"award-number":["2013\u00a0T042"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Netherlands Organization for Scientific Research","award":["825.13.007"],"award-info":[{"award-number":["825.13.007"]}]},{"name":"ZonMw VENI","award":["016.166.150"],"award-info":[{"award-number":["016.166.150"]}]},{"DOI":"10.13039\/100018703","name":"European Innovation Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018703","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Aviesan-ITMO Genetique-Genomique-Bioinformatique"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Dilated cardiomyopathy (DCM) is a major cause of heart failure (HF) defined by ventricular dilatation and systolic dysfunction. Although microRNAs (miRNAs) are known to affect HF development, little is known about the contribution of genetic variants in miRNAs or their precursors to the susceptibility or pathogenesis of DCM. We screened 1640 DCM cases for variants in cardiac miR-208a and miR-208b and their precursors. We identified four variants in the miR-208a pre-miRNA, which are present at very low frequencies in the general population. Two of these variants (+42G\u2009&amp;gt;\u2009T and\u2009+68G\u2009&amp;gt;\u2009T) alter a highly conserved nucleotide and the predicted pre-miRNA secondary structure. Both variants result in reduced mature miR-208a levels in overexpression experiments. The variant +42G\u2009&amp;gt;\u2009T also increased pre-miR-208a levels in these experiments, which indicates a maturation deficiency. Co-transfection of the overexpression constructs with a luciferase construct containing six miRNA binding sites revealed that both variants also impair repression of luciferase expression by miR-208a, indicative of also a loss of miR208a function. Together this indicates that these DCM-associated variants impair formation of mature miR208a. Combined with the role of miR-208a in cardiac contractility this suggests that variants +42G\u2009&amp;gt;\u2009T and\u2009+68G\u2009&amp;gt;\u2009T in pre-miR-208a may contribute to the DCM phenotype observed in these patients.<\/jats:p>","DOI":"10.1093\/hmg\/ddaf069","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T21:29:10Z","timestamp":1746566950000},"page":"1216-1226","source":"Crossref","is-referenced-by-count":1,"title":["Rare DCM associated variants in pre-miR-208a disrupt miRNA maturation and function"],"prefix":"10.1093","volume":"34","author":[{"given":"Yolan J","family":"Reckman","sequence":"first","affiliation":[{"name":"Amsterdam UMC, University of Amsterdam, Experimental Cardiology, Amsterdam Cardiovascular Sciences , Meibergdreef 9, 1105 AZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Haas","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Medical Faculty, Heidelberg University , Im Neuenheimer Feld 672, 69120 Heidelberg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingeborg","family":"van der Made","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, University of Amsterdam, Experimental Cardiology, Amsterdam Cardiovascular Sciences , Meibergdreef 9, 1105 AZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon G","family":"Williams","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, University of Manchester , Oxford Rd, Manchester M13 9PL ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iria Gomez","family":"Diaz","sequence":"additional","affiliation":[{"name":"Scientific Department, Health in Code S.L., Av. de Arteixo 43, 15008 A Coru\u00f1a,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Akhtar","sequence":"additional","affiliation":[{"name":"Inherited Cardiac Diseases Unit, The Heart Hospital, University College London , Gower St, London WC1E 6BT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Mogensen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Odense University Hospital , J. B. Winsl\u00f8ws Vej 4, 5000 Odense ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten B","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Aarhus Universitetshospital , Palle Juul-Jensens Boulevard 69, 8200 Aarhus ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Villard","sequence":"additional","affiliation":[{"name":"AP-HP, Department of Cardiology & Department of Genetics, Sorbonne University, INSERM UMRS-1166, ICAN Institute, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, 47-83 Bd de l'H\u00f4pital, 75013 Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Charron","sequence":"additional","affiliation":[{"name":"AP-HP, Department of Cardiology & Department of Genetics, Sorbonne University, INSERM UMRS-1166, ICAN Institute, Piti\u00e9-Salp\u00eatri\u00e8re Hospital , 47-83 Bd de l'H\u00f4pital, 75013 Paris ,","place":["France"]},{"name":"Member of the European Reference Network for rare , low prevalence and complex diseases of the heart: ERN GUARD-Heart"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perry","family":"Elliott","sequence":"additional","affiliation":[{"name":"Inherited Cardiac Diseases Unit, The Heart Hospital, University College London , Gower St, London WC1E 6BT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard D","family":"Keavney","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, University of Manchester , Oxford Rd, Manchester M13 9PL ,","place":["United Kingdom"]},{"name":"Medical Department, Dilemma Solutions SL , R\u00faa Antonio Insua Rivas, 56, 15008 A Coru\u00f1a,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Monserrat","sequence":"additional","affiliation":[{"name":"Manchester NIHR Biomedical Research Centre, Manchester University NHS Foundation Trust , Oxford Rd, Manchester M13 9WL ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yigal M","family":"Pinto","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, University of Amsterdam, Experimental Cardiology, Amsterdam Cardiovascular Sciences , Meibergdreef 9, 1105 AZ Amsterdam ,","place":["The Netherlands"]},{"name":"Member of the European Reference Network for rare , low prevalence and complex diseases of the heart: ERN GUARD-Heart"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Meder","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Medical Faculty, Heidelberg University , Im Neuenheimer Feld 672, 69120 Heidelberg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke J","family":"Tijsen","sequence":"additional","affiliation":[{"name":"Amsterdam 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