
Genetics of cardiac arrhythmia disorders and sudden death
Julien Barc and Vincent Probst
The primary objective of our group is to improve healthcare by combining basic research and clinical activity into translational research programs. Taking advantage of large pedigrees and one of the largest worldwide cohorts of patients suffering from inherited cardiac electrical disorders (Brugada syndrome, the long and short QT syndrome, the catecholaminergic polymorphic ventricular tachycardia, conduction defects, sinus dysfunction, idiopathic ventricular fibrillation and arrhythmogenic cardiomyopathy) we apply multi-omics screening strategies to establish clinical and genetic risk stratification for developing cardiac arrhythmia and prevent sudden cardiac death (SCD). The identification of new clinical and molecular markers from these ‘sensitized’ models of SCD are likely relevant to the broad problem of SCD.
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- REGIOCARD project
Our strategy based on whole genome screening allows us to open unique opportunities to interrogate the full spectrum genetic variations. Furthermore we are particularly interested in investigating the role of variants in the non-coding regions of the genome, seat of the gene regulation. We then developed the REGIOCARD program on cardiac epigenetics to functionally annotate the human cardiac regulatory regions.
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- LEARN project
- European Joint Programme on Rare Diseases: LQTS-NEXT
- International research partnership GAINES
Our research takes place in a context of international collaborations allowing young scientists to interact with the world leaders in the field, follow training to acquire new skills and develop their network.
Publications
- RRAD mutation causes electrical and cytoskeletal defects in cardiomyocytes derived from a familial case of Brugada syndrome. Belbachir N, Portero V, Al Sayed ZR, Gourraud J-B, Dilasser F, Jesel L, Guo H, Wu H, Gaborit N, Guilluy C, Girardeau A, Bonnaud S, Simonet F, Karakachoff M, Pattier S, Scott C, Burel S, Marionneau C, Chariau C, Gaignerie A, David L, Genin E, Deleuze J-F, Dina C, Sauzeau V, Loirand G, Baró I, Schott J-J, Probst V, Wu JC, Redon R, Charpentier F, Le Scouarnec S. Eur Heart J. 2019;doi:10.1093/eurheartj/ehz308.
- Progressive Atrial Conduction Defects Associated With Bone Malformation Caused by a Connexin-45 Mutation. Seki* A, Ishikawa* T, Daumy* X, Mishima H, Barc J, Sasaki R, Nishii K, Saito K, Urano M, Ohno S, Otsuki S, Kimoto H, Baruteau A-E, Thollet A, Fouchard S, Bonnaud S, Parent P, Shibata Y, Perrin J-P, Le Marec H, Hagiwara N, Mercier S, Horie M, Probst V, Yoshiura* K-I, Redon* R, Schott* J-J, Makita* N. J Am Coll Cardiol 2017;70:358–370.
- Familial Catecholamine-Induced QT Prolongation in Unexplained Sudden Cardiac Death. Huchet* F, Kyndt* F, Barc* J, Thollet A, Charpentier F, Redon R, Schott JJ, le Marec H, Probst V, Gourraud JB. J Am Coll Cardiol 2017;69:1642–1643.
- Testing the burden of rare variation in arrhythmia-susceptibility genes provides new insights into molecular diagnosis for Brugada syndrome. Le Scouarnec* S, Karakachoff* M, Gourraud* J-B, Lindenbaum P, Bonnaud S, Portero V, Duboscq-Bidot L, Daumy X, Simonet F, Teusan R, Baron E, Violleau J, Persyn E, Bellanger L, Barc J, Chatel S, Martins R, Mabo P, Sacher F, Haïssaguerre M, Kyndt F, Schmitt S, Bézieau S, Le Marec H, Dina C, Schott J-J, Probst V, Redon R. Hum Mol Genet 2015;24:2757–2763.
- Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death. Bezzina CR, Barc J, Mizusawa Y, Remme CA, Gourraud J-B, Simonet F, [...], Wilde AA*, Probst V*, Schott JJ*, Dina C*, Redon R*. Nat Genet 2013;45:1044–1049.
Funding
This programme has been financed by :
- Agence Nationale Recherche
- Boston Scientific
- CHU de Nantes
- Direction Générale de l'Offre de soin (PHRC-I)
- European Commission (H2020-MSCA-IF-2014 - RISTRAD-661617)
- Fédération Française de Cardiologie
- Fondation Cœur et Recherche
- Fondation Genavie
- Fondation Maladies Rares
- Fondation pour la Recherche médicale (DEQ20140329545)
- GCS HUGO
- Région des Pays de la Loire (REGIOCARD)
- Société Française de Cardiologie
- European Joint Programme on Rare Diseases