Skip Navigation


European Heart Journal Advance Access originally published online on June 12, 2009
European Heart Journal 2009 30(17):2128-2136; doi:10.1093/eurheartj/ehp225
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
30/17/2128    most recent
ehp225v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Duboscq-Bidot, L.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Duboscq-Bidot, L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org

Mutations in the ANKRD1 gene encoding CARP are responsible for human dilated cardiomyopathy

Laëtitia Duboscq-Bidot1,2, Philippe Charron1,2,3, Volker Ruppert4, Laurent Fauchier5, Anette Richter4, Luigi Tavazzi6, Eloisa Arbustini7, Thomas Wichter8, Bernard Maisch4, Michel Komajda1,2,9, Richard Isnard9, Eric Villard1,2,10,* on behalf of the EUROGENE Heart Failure Network

1 INSERM, U621, Paris F-75013, France
2 Université Pierre et Marie Curie Paris 6, IFR14, UMR-S956, Paris, France
3 Département de Génétique, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France
4 Klinik für Kardiologie, Universitätsklinikum Gießen und Marburg GmbH, Marburg, Germany
5 Cardiologie, Centre Hospitalier Universitaire Trousseau, Tours, France
6 GVM Hospitals of Care and Research, Cotignola, Italy
7 Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
8 Department of Cardiology and Angiology, University Hospital Münster, Münster, Germany
9 Département de Cardiologie, Institut de Cardiologie, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France
10 Centre d'Investigation Biomédicale Pitié-Salpêtrière, AP-HP, Paris, France

Received 29 November 2008; revised 1 April 2009; accepted 6 May 2009; online publish-ahead-of-print 12 June 2009.

* Corresponding author. Tel: +33 1 40 77 96 49, Fax: +33 1 40 77 96 45, Email: eric.villard{at}upmc.fr

Aims: Dilated cardiomyopathy (DCM) is familial in ~30% of cases, and mutations have been identified in several genes. However, in a majority of familial cases, the responsible genes are still to be discovered. The ANKRD1 gene is over-expressed in heart failure in human and animal models. The encoded protein CARP interacts with partners such as myopalladin or titin, previously shown to be involved in DCM. We hypothesized that mutations in ANKRD1 could be responsible for DCM.

Methods and results: We sequenced the coding region of ANKRD1 from 231 independent DCM cases. We identified five missense mutations (three sporadic and two familial) absent from 400 controls and affecting highly conserved residues. Expression of the mutant CARP proteins after transfection in rat neonate cardiomyocytes indicated that most of them led to both significantly less repressor activity measured in a reporter gene assay and greater phenylephrin-induced hypertrophy, suggesting altered function of CARP mutant proteins.

Conclusion: On the basis of genetic and functional analysis of CARP mutations, we have identified ANKRD1 as a new gene associated with DCM, accounting for ~2% of cases.

Key Words: ANKRD1 • Dilated cardiomyopathy • Gene • Cardiomyocyte • CARP • Mutation


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.