Skip to Main content Skip to Navigation
Journal articles

Genetic association analyses highlight biological pathways underlying mitral valve prolapse

Christian Dina 1, 2 Nabila Bouatia-Naji 3 Nathan Tucker Francesca N. Delling Katelynn Toomer Ronen Durst Maelle Perrocheau 3 Leticia Fernandez-Friera Jorge Solis Thierry Le Tourneau 1 Ming-Huei Chen Vincent Probst 1 Yohan Bosse Philippe Pibarot 4 Diana Zelenika 5 Mark Lathrop 5 Serge Hercberg 6, 7 Ronan Roussel 8 Emelia J. Benjamin Fabrice Bonnet 9 Su Hao Lo Elena Dolmatova Floriane Simonet 1 Simon Lecointe 1 Florence Kyndt 1 Richard Redon 1 Hervé Le Marec 1 Philippe Froguel 10, 11 Patrick T. Ellinor Ramachandran S. Vasan Patrick Bruneval 12, 13 Roger R. Markwald Russell A. Norris David J. Milan Susan A. Slaugenhaupt Robert A. Levine Jean-Jacques Schott 1 Albert A. Hagege Xavier Jeunemaitre 3, 14, 13
Abstract : Nonsyndromic mitral valve prolapse (MVP) is a common degenerative cardiac valvulopathy of unknown etiology that predisposes to mitral regurgitation, heart failure and sudden death. Previous family and pathophysiological studies suggest a complex pattern of inheritance. We performed a meta-analysis of 2 genome-wide association studies in 1,412 MVP cases and 2,439 controls. We identified 6 loci, which we replicated in 1,422 cases and 6,779 controls, and provide functional evidence for candidate genes. We highlight LMCD1 (LIM and cysteine-rich domains 1), which encodes a transcription factor and for which morpholino knockdown of the ortholog in zebrafish resulted in atrioventricular valve regurgitation. A similar zebrafish phenotype was obtained with knockdown of the ortholog of TNS1, which encodes tensin 1, a focal adhesion protein involved in cytoskeleton organization. We also showed expression of tensin 1 during valve morphogenesis and describe enlarged posterior mitral leaflets in Tns1(-/-) mice. This study identifies the first risk loci for MVP and suggests new mechanisms involved in mitral valve regurgitation, the most common indication for mitral valve repair
Complete list of metadata

Cited literature [29 references]  Display  Hide  Download
Contributor : Laurent Jonchère <>
Submitted on : Wednesday, July 11, 2018 - 9:11:24 AM
Last modification on : Friday, May 28, 2021 - 3:39:43 AM
Long-term archiving on: : Friday, October 12, 2018 - 12:11:11 PM


Files produced by the author(s)



Christian Dina, Nabila Bouatia-Naji, Nathan Tucker, Francesca N. Delling, Katelynn Toomer, et al.. Genetic association analyses highlight biological pathways underlying mitral valve prolapse. Nature Genetics, Nature Publishing Group, 2015, 47 (10), pp.1206-1211. ⟨10.1038/ng.3383⟩. ⟨hal-01191656⟩



Record views


Files downloads