ArticleNature2015
Mutations in DCHS1 cause mitral valve prolapse.
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Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 1 of them a synthesis that pooled it.
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116citing papers in PubMed, 1 pooled it
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Who cites it
116 citing papers in PubMed, 1 synthesis or guideline pooled it, 198 citations in OpenAlex.
- Genome-wide association study reveals novel genetic loci: a new polygenic risk score for mitral valve prolapse.European heart journal · 2022Pooled it
- Regional strain patterns in patients with mitral valve prolapse.Clinical research in cardiology : official journal of the German Cardiac Society · 2026Article
- Human iPSC-derived heart valve-like assembloids model valve development and disease pathology.Cell stem cell · 2026Article
- Giant Right Atrial Aneurysm: Observation Versus Intervention.JACC. Case reports · 2026Article
- Dachsous-Fat signaling shapes the Drosophila wing through mechanical forces.PLoS biology · 2026Article
- Article
- Floppy Mitral Valve/Mitral Valve Prolapse: Diagnosis and Clinical Classification in This Continuing Odyssey.European cardiology · 2026Review
- Recent advances in omics-based research of mitral valve disease.Frontiers in cardiovascular medicine · 2026Review
- Mitral Annular Disjunction and Coalescing Myths in Cardiology.Arrhythmia & electrophysiology review · 2026Article
- Mechanisms of mitral valve development and disease.Frontiers in cardiovascular medicine · 2026Review
- Connective tissue disorders and cardiac arrhythmias: genetic pathways, mechanistic bridges, and clinical implications.Frontiers in cardiovascular medicine · 2026Review
- Whole exome sequencing of 80 cases of sporadic mitral valve prolapse reveals novel disease-associated genes and variants in a Southern Chinese population.Genes & genomics · 2025Article
- Dynamic Expression and Functional Implications of the Cell Polarity Gene, Dchs1, During Cardiac Development.Cells · 2025Article
- Gut Microbial Metabolite Imidazole Propionate Impairs Endothelial Cell Function and Promotes the Development of Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- AClinical case reports · 2025Article
- 2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.Circulation · 2025Review
- Genetic Background and Clinical Phenotype in an Italian Cohort with Inherited Arrhythmia Syndromes and Arrhythmogenic Cardiomyopathy (ACM): A Whole-Exome Sequencing Study.International journal of molecular sciences · 2025Article
- Characterization of LTBP2 mutation causing mitral valve prolapse.European heart journal open · 2025Article
- Interacting Fat1 and Dchs Planar Cell Polarity Proteins Supported by Fjx1 Serve as Heterodimeric Intercellular Bridges Crucial to Support Spermatogenesis.Advances in experimental medicine and biology · 2025Review
- Contributions of the Dachsous intracellular domain to Dachsous-Fat signaling.Development (Cambridge, England) · 2024Article
56 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
50 authors at 20 institutions in 4 countries.
Ronen DurstCenter for Human Genetic Research, Massachusetts General Hospital Research Institute and Department of Neurology, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114 USA.
Kimberly SaulsCardiovascular Developmental Biology Center, Department of Regenerative Medicine and Cell Biology, Department of Medicine, Children's Research Institute, Medical University of South Carolina, 171 Ashley Avenue, Charleston, South Carolina 29425, USA.
David S PealCardiovascular Research Center, Cardiology Division, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, Massachusetts 02114, USA.
Annemarieke deVlamingCardiovascular Developmental Biology Center, Department of Regenerative Medicine and Cell Biology, Department of Medicine, Children's Research Institute, Medical University of South Carolina, 171 Ashley Avenue, Charleston, South Carolina 29425, USA.
Katelynn ToomerCardiovascular Developmental Biology Center, Department of Regenerative Medicine and Cell Biology, Department of Medicine, Children's Research Institute, Medical University of South Carolina, 171 Ashley Avenue, Charleston, South Carolina 29425, USA.
Maire LeyneCenter for Human Genetic Research, Massachusetts General Hospital Research Institute and Department of Neurology, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114 USA.
Monica SalaniCenter for Human Genetic Research, Massachusetts General Hospital Research Institute and Department of Neurology, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114 USA.
Michael E TalkowskiCenter for Human Genetic Research, Massachusetts General Hospital Research Institute and Department of Neurology, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114 USA.
Harrison BrandCenter for Human Genetic Research, Massachusetts General Hospital Research Institute and Department of Neurology, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114 USA.
Maëlle PerrocheauINSERM, UMR-970, Paris Cardiovascular Research Center, 75015 Paris, France.
Charles SimpsonCenter for Human Genetic Research, Massachusetts General Hospital Research Institute and Department of Neurology, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114 USA.
Christopher JettCenter for Human Genetic Research, Massachusetts General Hospital Research Institute and Department of Neurology, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114 USA.
Matthew R StoneCenter for Human Genetic Research, Massachusetts General Hospital Research Institute and Department of Neurology, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114 USA.
Florie CharlesCenter for Human Genetic Research, Massachusetts General Hospital Research Institute and Department of Neurology, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114 USA.
Colby ChiangCenter for Human Genetic Research, Massachusetts General Hospital Research Institute and Department of Neurology, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114 USA.
Stacey N LynchCardiovascular Research Center, Cardiology Division, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, Massachusetts 02114, USA.
Nabila Bouatia-NajiINSERM, UMR-970, Paris Cardiovascular Research Center, 75015 Paris, France.
Francesca N DellingDepartment of Medicine (Cardiovascular Division), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Lisa A FreedYale-New Haven Hospital Heart and Vascular Center, Yale School of Medicine, 20 York Street, New Haven, Connecticut 06510, USA.
Christophe TribouilloyDepartment of Cardiology, University Hospital Amiens; INSERM U-1088, Jules Verne University of Picardie, 80000 Amiens, France.
Thierry Le TourneauInserm U1087; Institut du Thorax; University Hospital, 44007 Nantes, France.
Hervé LeMarecInserm U1087; Institut du Thorax; University Hospital, 44007 Nantes, France.
Leticia Fernandez-FrieraCentro Nacional de Investigaciones Cardiovasculares, Carlos III (CNIC), 28029 Madrid, Spain.
Jorge SolisCentro Nacional de Investigaciones Cardiovasculares, Carlos III (CNIC), 28029 Madrid, Spain.
Daniel TrujillanoGenetic Causes of Disease Group, Centre for Genomic Regulation (CRG), 08003 Barcelona, Catalonia, Spain.
Stephan OssowskiUniversitat Pompeu Fabra (UPF), 08002 Barcelona, Catalonia, Spain.
Xavier EstivillGenetic Causes of Disease Group, Centre for Genomic Regulation (CRG), 08003 Barcelona, Catalonia, Spain.
Christian DinaInserm U1087; Institut du Thorax; University Hospital, 44007 Nantes, France.
Patrick BrunevalService d'Anatomie Pathologique, Hôpital Européen Georges Pompidou, 75015 Paris, France.
Adrian ChesterNational Heart and Lung Institute, Harefield, Heart Science Centre, Imperial College London, London SW7 2AZ, UK.
Jean-Jacques SchottInserm U1087; Institut du Thorax; University Hospital, 44007 Nantes, France.
Kenneth D IrvineHoward Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers, the State University of New Jersey, Piscataway, New Jersey 08854, USA.
Yaopan MaoHoward Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers, the State University of New Jersey, Piscataway, New Jersey 08854, USA.
Andy WesselsCardiovascular Developmental Biology Center, Department of Regenerative Medicine and Cell Biology, Department of Medicine, Children's Research Institute, Medical University of South Carolina, 171 Ashley Avenue, Charleston, South Carolina 29425, USA.
Tahirali MotiwalaCardiovascular Developmental Biology Center, Department of Regenerative Medicine and Cell Biology, Department of Medicine, Children's Research Institute, Medical University of South Carolina, 171 Ashley Avenue, Charleston, South Carolina 29425, USA.
Michel PuceatINSERM UMR_S910, Team physiopathology of cardiac development Aix-Marseille University, Medical School La Timone, 13885 Marseille, France.
Yoshikazu TsukasakiDepartment of Cellular and Molecular Biology, University of Texas Health Science Center Northeast Tyler, Texas75708, USA.
Donald R MenickGazes Cardiac Research Institute, Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Harinath KasiganesanGazes Cardiac Research Institute, Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Xingju NieDepartment of Radiology and Radiological Sciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Ann-Marie BroomeDepartment of Radiology and Radiological Sciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Katherine WilliamsCardiovascular Developmental Biology Center, Department of Regenerative Medicine and Cell Biology, Department of Medicine, Children's Research Institute, Medical University of South Carolina, 171 Ashley Avenue, Charleston, South Carolina 29425, USA.
Amanda JohnsonCardiovascular Developmental Biology Center, Department of Regenerative Medicine and Cell Biology, Department of Medicine, Children's Research Institute, Medical University of South Carolina, 171 Ashley Avenue, Charleston, South Carolina 29425, USA.
Roger R MarkwaldCardiovascular Developmental Biology Center, Department of Regenerative Medicine and Cell Biology, Department of Medicine, Children's Research Institute, Medical University of South Carolina, 171 Ashley Avenue, Charleston, South Carolina 29425, USA.
Xavier JeunemaitreINSERM, UMR-970, Paris Cardiovascular Research Center, 75015 Paris, France.
Albert HagegeINSERM, UMR-970, Paris Cardiovascular Research Center, 75015 Paris, France.
Robert A LevineUniversité Paris Descartes, Sorbonne Paris Cité, Faculty of Medicine, 75006 Paris, France.
David J MilanCenter for Human Genetic Research, Massachusetts General Hospital Research Institute and Department of Neurology, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114 USA.
Russell A NorrisCardiovascular Developmental Biology Center, Department of Regenerative Medicine and Cell Biology, Department of Medicine, Children's Research Institute, Medical University of South Carolina, 171 Ashley Avenue, Charleston, South Carolina 29425, USA.
Susan A SlaugenhauptCenter for Human Genetic Research, Massachusetts General Hospital Research Institute and Department of Neurology, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114 USA.
Medical University of South Carolina · USMassachusetts General Hospital · USInserm · FRCenter for Systems Biology · USCenter for Human Genetics · USHarvard University · USParis Cardiovascular Research Center · FRSpanish National Centre for Cardiovascular Research · ESBeth Israel Deaconess Medical Center · USCentre for Genomic Regulation · ESDélégation Paris 5 · FRHôpital Européen · FRHospital del Mar Research Institute · ESHoward Hughes Medical Institute · USImperial College London · GBInstitut du Thorax · FRPompeu Fabra University · ESRutgers, The State University of New Jersey · USThe University of Texas Health Science Center at Tyler · USUniversité de Picardie Jules Verne · FR
Funding
MULTIDISCIPLINARY RESEARCH TRAINING IN CARDIOLOGYT32HL007208 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Patrick Thomas Ellinor, David E Sosnovik · 1985 to 2026
$16.1MTargeted Nano-therapeutics for Neural RegenerationP20GM103444 · NIGMS · CLEMSON UNIVERSITY · PI NORRIS, RUSSELL · 2012 to 2018
$14.9MTRAINING TO IMPROVE CARDIOVASCULAR THERAPIEST32HL007260 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI MENICK, DONALD R. · 1985 to 2021
$11.1MSC COBRE for Developmentally Based Cardiovascular DiseasesP30GM103342 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI KERN, MICHAEL J · 2012 to 2016
$5.5MMUCOPOLYSACCHRIDE METABOLISM IN CARDIAC ANOMALIESR01HL033756 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI MARKWALD, ROGER R · 1985 to 2015
$4.8MMechanisms of DMP Development and Atrioventricular SeptationR01HL122906 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI WESSELS, ARNO · 2015 to 2025
$4.3MEffect of Mitral Regurgitation on Ischemic LV RemodelingR01HL072265 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI LEVINE, ROBERT A · 2003 to 2013
$3.5MImproving Mitral Compensation in Ischemic RegurgitationR01HL109506 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI AIKAWA, ELENA, BISCHOFF, JOYCE E. · 2012 to 2015
$3.3MGenetics and Mechanisms of Mitral Valve ProlapseR01HL127692 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI MILAN, DAVID J, SLAUGENHAUPT, SUSAN A · 2015 to 2018
$3.0MEXTRAMURAL RESEARCH FACILITIES CONSTRUCTIONC06RR018823 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND, JOHN R · 2003 to 2003
$2.9MTreating Ventricle and Valve: New Synergies for Ischemic LV Remodeling with MRR01HL128099 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI AKAR, FADI GABRIEL, LEVINE, ROBERT A · 2016 to 2019
$2.8MISCHEMIC MITRAL REGURGITATION: FROM MECHANISM TO THERAPYK24HL067434 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI LEVINE, ROBERT A · 2001 to 2011
$1.6MBLRD VA I01 BX002327Howard Hughes Medical InstituteNCRR NIH HHS C06 RR018823NHLBI NIH HHS K23 HL116652NHLBI NIH HHS K24 HL067434NHLBI NIH HHS K24 HL67434NHLBI NIH HHS R01 HL033756NHLBI NIH HHS R01 HL072265NHLBI NIH HHS R01 HL095696NHLBI NIH HHS R01-HL095696NHLBI NIH HHS R01 HL109004NHLBI NIH HHS R01-HL109004NHLBI NIH HHS R01 HL109506NHLBI NIH HHS R01HL109506NHLBI NIH HHS R01 HL122906NHLBI NIH HHS R01HL122906-01NHLBI NIH HHS R01 HL127692NHLBI NIH HHS R01-HL127692NHLBI NIH HHS R01 HL128099NHLBI NIH HHS R01-HL33756NHLBI NIH HHS R01HL72265NHLBI NIH HHS T32 HL007208NHLBI NIH HHS T32 HL007260NIGMS NIH HHS 1P30 GM103342NIGMS NIH HHS 8P20 GM103444-07NIGMS NIH HHS P20 GM103444NIGMS NIH HHS P30 GM103342NIMH NIH HHS K99 MH095867NIMH NIH HHS R00 MH095867NIMH NIH HHS R00-MH095867
Abstract
Mitral valve prolapse (MVP) is a common cardiac valve disease that affects nearly 1 in 40 individuals. It can manifest as mitral regurgitation and is the leading indication for mitral valve surgery. Despite a clear heritable component, the genetic aetiology leading to non-syndromic MVP has remained elusive. Four affected individuals from a large multigenerational family segregating non-syndromic MVP underwent capture sequencing of the linked interval on chromosome 11. We report a missense mutation in the DCHS1 gene, the human homologue of the Drosophila cell polarity gene dachsous (ds), that segregates with MVP in the family. Morpholino knockdown of the zebrafish homologue dachsous1b resulted in a cardiac atrioventricular canal defect that could be rescued by wild-type human DCHS1, but not by DCHS1 messenger RNA with the familial mutation. Further genetic studies identified two additional families in which a second deleterious DCHS1 mutation segregates with MVP. Both DCHS1 mutations reduce protein stability as demonstrated in zebrafish, cultured cells and, notably, in mitral valve interstitial cells (MVICs) obtained during mitral valve repair surgery of a proband. Dchs1(+/-) mice had prolapse of thickened mitral leaflets, which could be traced back to developmental errors in valve morphogenesis. DCHS1 deficiency in MVP patient MVICs, as well as in Dchs1(+/-) mouse MVICs, result in altered migration and cellular patterning, supporting these processes as aetiological underpinnings for the disease. Understanding the role of DCHS1 in mitral valve development and MVP pathogenesis holds potential for therapeutic insights for this very common disease.
Indexed as
AnimalsBody PatterningCadherin Related ProteinsCadherinsCell MovementChromosomes, Human, Pair 11FemaleHumansMaleMiceMitral ValveMitral Valve ProlapseMutationPedigreePhenotypeProtein StabilityCadherin Related ProteinsCadherinsDCHS1b protein, zebrafishDCHS1 protein, humanDchs1 protein, mouseRNA, MessengerZebrafish Proteins
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