Search

Your search keyword '"Baron, Estelle"' showing total 47 results
Start Over Author "Baron, Estelle"

Refine your results

47 results on '"Baron, Estelle"'

1. Human genetic structure in Northwest France provides new insights into West European historical demography

Author

Alves, Isabel, Giemza, Joanna, Blum, Michael G. B., Bernhardsson, Carolina, Chatel, Stéphanie, Karakachoff, Matilde, Saint Pierre, Aude, Herzig, Anthony F., Olaso, Robert, Monteil, Martial, Gallien, Véronique, Cabot, Elodie, Svensson, Emma, Bacq, Delphine, Baron, Estelle, Berthelier, Charlotte, Besse, Céline, Blanché, Hélène, Bocher, Ozvan, Boland, Anne, Bonnaud, Stéphanie, Charpentier, Eric, Dandine-Roulland, Claire, Férec, Claude, Fruchet, Christine, Lecointe, Simon, Le Floch, Edith, Ludwig, Thomas E., Marenne, Gaëlle, Meyer, Vincent, Quellery, Elisabeth, Racimo, Fernando, Rouault, Karen, Sandron, Florian, Schott, Jean-Jacques, Velo-Suarez, Lourdes, Violleau, Jade, Willerslev, Eske, Coativy, Yves, Jézéquel, Mael, Le Bris, Daniel, Nicolas, Clément, Pailler, Yvan, Goldberg, Marcel, Zins, Marie, Le Marec, Hervé, Jakobsson, Mattias, Darlu, Pierre, Génin, Emmanuelle, Deleuze, Jean-François, Redon, Richard, and Dina, Christian

Published
2024
Full Text
View/download PDF

2. TAD boundary deletion causes PITX2-related cardiac electrical and structural defects

Author

Baudic, Manon, Murata, Hiroshige, Bosada, Fernanda M., Melo, Uirá Souto, Aizawa, Takanori, Lindenbaum, Pierre, van der Maarel, Lieve E., Guedon, Amaury, Baron, Estelle, Fremy, Enora, Foucal, Adrien, Ishikawa, Taisuke, Ushinohama, Hiroya, Jurgens, Sean J., Choi, Seung Hoan, Kyndt, Florence, Le Scouarnec, Solena, Wakker, Vincent, Thollet, Aurélie, Rajalu, Annabelle, Takaki, Tadashi, Ohno, Seiko, Shimizu, Wataru, Horie, Minoru, Kimura, Takeshi, Ellinor, Patrick T., Petit, Florence, Dulac, Yves, Bru, Paul, Boland, Anne, Deleuze, Jean-François, Redon, Richard, Le Marec, Hervé, Le Tourneau, Thierry, Gourraud, Jean-Baptiste, Yoshida, Yoshinori, Makita, Naomasa, Vieyres, Claude, Makiyama, Takeru, Mundlos, Stephan, Christoffels, Vincent M., Probst, Vincent, Schott, Jean-Jacques, and Barc, Julien

Published
2024
Full Text
View/download PDF

3. Intercomparison of opto-thermal spectral measurements for concentrating solar thermal receiver materials from room temperature up to 800 °C

Author

Caron, Simon, Farchado, Meryem, San Vicente, Gema, Morales, Angel, Ballestrín, Jesus, Carvalho, Maria Joao, Pascoa, Soraia, le Baron, Estelle, Disdier, Angela, Guillot, Emmanuel, Escape, Christophe, Sans, Jean-Louis, Binyamin, Yaniv, Baidossi, Mubeen, Sutter, Florian, Röger, Marc, and Manzano-Agugliaro, Francisco

Published
2024
Full Text
View/download PDF

4. Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility

Author

Barc, Julien, Tadros, Rafik, Glinge, Charlotte, Chiang, David Y., Jouni, Mariam, Simonet, Floriane, Jurgens, Sean J., Baudic, Manon, Nicastro, Michele, Potet, Franck, Offerhaus, Joost A., Walsh, Roddy, Choi, Seung Hoan, Verkerk, Arie O., Mizusawa, Yuka, Anys, Soraya, Minois, Damien, Arnaud, Marine, Duchateau, Josselin, Wijeyeratne, Yanushi D., Muir, Alison, Papadakis, Michael, Castelletti, Silvia, Torchio, Margherita, Ortuño, Cristina Gil, Lacunza, Javier, Giachino, Daniela F., Cerrato, Natascia, Martins, Raphaël P., Campuzano, Oscar, Van Dooren, Sonia, Thollet, Aurélie, Kyndt, Florence, Mazzanti, Andrea, Clémenty, Nicolas, Bisson, Arnaud, Corveleyn, Anniek, Stallmeyer, Birgit, Dittmann, Sven, Saenen, Johan, Noël, Antoine, Honarbakhsh, Shohreh, Rudic, Boris, Marzak, Halim, Rowe, Matthew K., Federspiel, Claire, Le Page, Sophie, Placide, Leslie, Milhem, Antoine, Barajas-Martinez, Hector, Beckmann, Britt-Maria, Krapels, Ingrid P., Steinfurt, Johannes, Winkel, Bo Gregers, Jabbari, Reza, Shoemaker, Moore B., Boukens, Bas J., Škorić-Milosavljević, Doris, Bikker, Hennie, Manevy, Federico C., Lichtner, Peter, Ribasés, Marta, Meitinger, Thomas, Müller-Nurasyid, Martina, Veldink, Jan H., van den Berg, Leonard H., Van Damme, Philip, Cusi, Daniele, Lanzani, Chiara, Rigade, Sidwell, Charpentier, Eric, Baron, Estelle, Bonnaud, Stéphanie, Lecointe, Simon, Donnart, Audrey, Le Marec, Hervé, Chatel, Stéphanie, Karakachoff, Matilde, Bézieau, Stéphane, London, Barry, Tfelt-Hansen, Jacob, Roden, Dan, Odening, Katja E., Cerrone, Marina, Chinitz, Larry A., Volders, Paul G., van de Berg, Maarten P., Laurent, Gabriel, Faivre, Laurence, Antzelevitch, Charles, Kääb, Stefan, Arnaout, Alain Al, Dupuis, Jean-Marc, Pasquie, Jean-Luc, Billon, Olivier, Roberts, Jason D., Jesel, Laurence, Borggrefe, Martin, Lambiase, Pier D., Mansourati, Jacques, Loeys, Bart, Leenhardt, Antoine, Guicheney, Pascale, Maury, Philippe, Schulze-Bahr, Eric, Robyns, Tomas, Breckpot, Jeroen, Babuty, Dominique, Priori, Silvia G., Napolitano, Carlo, de Asmundis, Carlo, Brugada, Pedro, Brugada, Ramon, Arbelo, Elena, Brugada, Josep, Mabo, Philippe, Behar, Nathalie, Giustetto, Carla, Molina, Maria Sabater, Gimeno, Juan R., Hasdemir, Can, Schwartz, Peter J., Crotti, Lia, McKeown, Pascal P., Sharma, Sanjay, Behr, Elijah R., Haissaguerre, Michel, Sacher, Frédéric, Rooryck, Caroline, Tan, Hanno L., Remme, Carol A., Postema, Pieter G., Delmar, Mario, Ellinor, Patrick T., Lubitz, Steven A., Gourraud, Jean-Baptiste, Tanck, Michael W., George, Jr., Alfred L., MacRae, Calum A., Burridge, Paul W., Dina, Christian, Probst, Vincent, Wilde, Arthur A., Schott, Jean-Jacques, Redon, Richard, and Bezzina, Connie R.

Published
2022
Full Text
View/download PDF

7. Author Correction: Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility

Author

Barc, Julien, Tadros, Rafik, Glinge, Charlotte, Chiang, David Y., Jouni, Mariam, Simonet, Floriane, Jurgens, Sean J., Baudic, Manon, Nicastro, Michele, Potet, Franck, Offerhaus, Joost A., Walsh, Roddy, Choi, Seung Hoan, Verkerk, Arie O., Mizusawa, Yuka, Anys, Soraya, Minois, Damien, Arnaud, Marine, Duchateau, Josselin, Wijeyeratne, Yanushi D., Muir, Alison, Papadakis, Michael, Castelletti, Silvia, Torchio, Margherita, Ortuño, Cristina Gil, Lacunza, Javier, Giachino, Daniela F., Cerrato, Natascia, Martins, Raphaël P., Campuzano, Oscar, Van Dooren, Sonia, Thollet, Aurélie, Kyndt, Florence, Mazzanti, Andrea, Clémenty, Nicolas, Bisson, Arnaud, Corveleyn, Anniek, Stallmeyer, Birgit, Dittmann, Sven, Saenen, Johan, Noël, Antoine, Honarbakhsh, Shohreh, Rudic, Boris, Marzak, Halim, Rowe, Matthew K., Federspiel, Claire, Le Page, Sophie, Placide, Leslie, Milhem, Antoine, Barajas-Martinez, Hector, Beckmann, Britt-Maria, Krapels, Ingrid P., Steinfurt, Johannes, Winkel, Bo Gregers, Jabbari, Reza, Shoemaker, Moore B., Boukens, Bas J., Škorić-Milosavljević, Doris, Bikker, Hennie, Manevy, Federico, Lichtner, Peter, Ribasés, Marta, Meitinger, Thomas, Müller-Nurasyid, Martina, Veldink, Jan H., van den Berg, Leonard H., Van Damme, Philip, Cusi, Daniele, Lanzani, Chiara, Rigade, Sidwell, Charpentier, Eric, Baron, Estelle, Bonnaud, Stéphanie, Lecointe, Simon, Donnart, Audrey, Le Marec, Hervé, Chatel, Stéphanie, Karakachoff, Matilde, Bézieau, Stéphane, London, Barry, Tfelt-Hansen, Jacob, Roden, Dan, Odening, Katja E., Cerrone, Marina, Chinitz, Larry A., Volders, Paul G., van de Berg, Maarten P., Laurent, Gabriel, Faivre, Laurence, Antzelevitch, Charles, Kääb, Stefan, Arnaout, Alain Al, Dupuis, Jean-Marc, Pasquie, Jean-Luc, Billon, Olivier, Roberts, Jason D., Jesel, Laurence, Borggrefe, Martin, Lambiase, Pier D., Mansourati, Jacques, Loeys, Bart, Leenhardt, Antoine, Guicheney, Pascale, Maury, Philippe, Schulze-Bahr, Eric, Robyns, Tomas, Breckpot, Jeroen, Babuty, Dominique, Priori, Silvia G., Napolitano, Carlo, de Asmundis, Carlo, Brugada, Pedro, Brugada, Ramon, Arbelo, Elena, Brugada, Josep, Mabo, Philippe, Behar, Nathalie, Giustetto, Carla, Molina, Maria Sabater, Gimeno, Juan R., Hasdemir, Can, Schwartz, Peter J., Crotti, Lia, McKeown, Pascal P., Sharma, Sanjay, Behr, Elijah R., Haissaguerre, Michel, Sacher, Frédéric, Rooryck, Caroline, Tan, Hanno L., Remme, Carol A., Postema, Pieter G., Delmar, Mario, Ellinor, Patrick T., Lubitz, Steven A., Gourraud, Jean-Baptiste, Tanck, Michael W., George, Jr., Alfred L., MacRae, Calum A., Burridge, Paul W., Dina, Christian, Probst, Vincent, Wilde, Arthur A., Schott, Jean-Jacques, Redon, Richard, and Bezzina, Connie R.

Published
2022
Full Text
View/download PDF

8. Targeted resequencing identifies TRPM4 as a major gene predisposing to progressive familial heart block type I

Author

Daumy, Xavier, Amarouch, Mohamed-Yassine, Lindenbaum, Pierre, Bonnaud, Stéphanie, Charpentier, Eric, Bianchi, Beatrice, Nafzger, Sabine, Baron, Estelle, Fouchard, Swanny, Thollet, Aurélie, Kyndt, Florence, Barc, Julien, Le Scouarnec, Solena, Makita, Naomasa, Le Marec, Hervé, Dina, Christian, Gourraud, Jean-Baptiste, Probst, Vincent, Abriel, Hugues, Redon, Richard, and Schott, Jean-Jacques

Published
2016
Full Text
View/download PDF

9. Intercomparison of Opto-Thermal Spectral Measurements for Concentrating Solar Thermal Receiver Materials from Room Temperature Up to 800 °C

Author

Caron, Simon, primary, Farchado, Meryem, additional, San Vicente, Gema, additional, Morales, Ángel, additional, Ballestrín, Jesús, additional, Carvalho, Maria Joao, additional, Pascoa, Soraia, additional, le Baron, Estelle, additional, Guillot, Emmanuel, additional, Escape, Christophe, additional, Sans, Jean-Louis, additional, Binyamin, Yaniv, additional, Baidossi, Mubeen, additional, Sutter, Florian, additional, Röger, Marc, additional, and Manzano-Agugliaro, Francisco, additional

Published
2023
Full Text
View/download PDF

10. Multimodality imaging and transcriptomics to phenotype mitral valve dystrophy in a unique knock-in Filamin-Arat model

Author

Delwarde, Constance, primary, Toquet, Claire, additional, Aumond, Pascal, additional, Kayvanjoo, Amir Hossein, additional, Foucal, Adrien, additional, Le Vely, Benjamin, additional, Baudic, Manon, additional, Lauzier, Benjamin, additional, Blandin, Stéphanie, additional, Véziers, Joëlle, additional, Paul-Gilloteaux, Perrine, additional, Lecointe, Simon, additional, Baron, Estelle, additional, Massaiu, Ilaria, additional, Poggio, Paolo, additional, Rémy, Séverine, additional, Anegon, Ignacio, additional, Le Marec, Hervé, additional, Monassier, Laurent, additional, Schott, Jean Jacques, additional, Mass, Elvira, additional, Barc, Julien, additional, Le Tourneau, Thierry, additional, Merot, Jean, additional, and Capoulade, Romain, additional

Published
2022
Full Text
View/download PDF

12. Burden of rare variants in arrhythmogenic cardiomyopathy with right dominant form‐associated genes provides new insights for molecular diagnosis and clinical management

Author

Goudal, Adeline, primary, Karakachoff, Matilde, additional, Lindenbaum, Pierre, additional, Baron, Estelle, additional, Bonnaud, Stéphanie, additional, Kyndt, Florence, additional, Arnaud, Marine, additional, Minois, Damien, additional, Bourcereau, Emmanuelle, additional, Thollet, Aurélie, additional, Deleuze, Jean‐François, additional, Genin, Emmanuelle, additional, Wiart, François, additional, Pasquié, Jean‐Luc, additional, Galand, Vincent, additional, Sacher, Frédéric, additional, Dina, Christian, additional, Redon, Richard, additional, Bezieau, Stéphane, additional, Schott, Jean‐Jacques, additional, Probst, Vincent, additional, and Barc, Julien, additional

Published
2022
Full Text
View/download PDF

13. Non-coding deletion induces 3D chromatin remodelling and PITX2 expression dysregulation associated with a new syndromic cardiac disorder

Author

Baudic, Manon, primary, Murata, Hiroshigue, additional, Bosada, Fernanda, additional, Melo, Uirá Souto, additional, Ishikawa, Taisuke, additional, Aizawa, Takanori, additional, Guedon, Amaury, additional, Baron, Estelle, additional, Foucal, Adrien, additional, Lindenbaum, Pierre, additional, Le Scouarnec, Solena, additional, Makita, Naomasa, additional, Le Marec, Hervé, additional, Vieyres, Claude, additional, Mundlos, Stephan, additional, Christoffels, Vincent M., additional, Makiyama, Takeru, additional, Probst, Vincent, additional, Schott, Jean-Jacques, additional, and Barc, Julien, additional

Published
2022
Full Text
View/download PDF

16. Multimodality imaging and transcriptomics to phenotype mitral valve dystrophy in a unique knock-in Filamin-A rat model.

Author

Delwarde, Constance, Toquet, Claire, Aumond, Pascal, Kayvanjoo, Amir Hossein, Foucal, Adrien, Vely, Benjamin Le, Baudic, Manon, Lauzier, Benjamin, Blandin, Stéphanie, Véziers, Joëlle, Paul-Gilloteaux, Perrine, Lecointe, Simon, Baron, Estelle, Massaiu, Ilaria, Poggio, Paolo, Rémy, Séverine, Anegon, Ignacio, Marec, Hervé Le, Monassier, Laurent, and Schott, Jean-Jacques

Subjects
MITRAL valve, ANIMAL disease models, DOPPLER echocardiography, DYSTROPHY, EXTRACELLULAR matrix, MITRAL valve prolapse
Abstract

Aims Degenerative mitral valve dystrophy (MVD) leading to mitral valve prolapse is the most frequent form of MV disease, and there is currently no pharmacological treatment available. The limited understanding of the pathophysiological mechanisms leading to MVD limits our ability to identify therapeutic targets. This study aimed to reveal the main pathophysiological pathways involved in MVD via the multimodality imaging and transcriptomic analysis of the new and unique knock-in (KI) rat model for the FilaminA-P637Q (FlnA-P637Q) mutation associated-MVD. Methods and results Wild-type (WT) and KI rats were evaluated morphologically, functionally, and histologically between 3-week-old and 3-to-6-month-old based on Doppler echocardiography, 3D micro-computed tomography (microCT), and standard histology. RNA-sequencing and Assay for Transposase-Accessible Chromatin (ATAC-seq) were performed on 3-week-old WT and KI mitral valves and valvular cells, respectively, to highlight the main signalling pathways associated with MVD. Echocardiographic exploration confirmed MV elongation (2.0 ± 0.1 mm vs. 1.8 ± 0.1, P = 0.001), as well as MV thickening and prolapse in KI animals compared to WT at 3 weeks. 3D MV volume quantified by microCT was significantly increased in KI animals (+58% vs. WT, P = 0.02). Histological analyses revealed a myxomatous remodelling in KI MV characterized by proteoglycans accumulation. A persistent phenotype was observed in adult KI rats. Signalling pathways related to extracellular matrix homeostasis, response to molecular stress, epithelial cell migration, endothelial to mesenchymal transition, chemotaxis and immune cell migration, were identified based on RNA-seq analysis. ATAC-seq analysis points to the critical role of transforming growth factor-β and inflammation in the disease. Conclusion The KI FlnA-P637Q rat model mimics human myxomatous MVD, offering a unique opportunity to decipher pathophysiological mechanisms related to this disease. Extracellular matrix organization, epithelial cell migration, response to mechanical stress, and a central contribution of immune cells are highlighted as the main signalling pathways leading to myxomatous MVD. Our findings pave the road to decipher underlying molecular mechanisms and the specific role of distinct cell populations in this context. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

17. BS-515-01 NON-CODING DELETION INDUCES 3D CHROMATIN REMODELLING AND PITX2 EXPRESSION DYSREGULATION ASSOCIATED WITH A SYNDROMIC CARDIAC DISORDER

Author

Baudic, Manon, primary, Murata, Hiroshige, additional, Bosada, Fernanda M., additional, Melo, Uira Souto, additional, Ishikawa, Taisuke, additional, Aizawa, Takanori, additional, Guedon, Amaury, additional, Baron, Estelle, additional, FOUCAL, ADRIEN, additional, Lindenbaum, Pierre, additional, Le Scouarnec, Solena, additional, Shimizu, Wataru, additional, GOURRAUD, JEAN BAPTISTE, additional, Makita, Naomasa, additional, Le Marec, Herve, additional, Vieyres, Claude, additional, Mundlos, Stephan, additional, Christoffels, Vincent M., additional, Makiyama, Takeru, additional, PROBST, VINCENT, additional, Schott, Jean-Jacques, additional, and Barc, Julien, additional

Published
2022
Full Text
View/download PDF

18. Genetic population structure across Brittany and the downstream Loire basin provides new insights on the demographic history of Western Europe

Author

Alves, Isabel, primary, Giemza, Joanna, additional, Blum, Michael, additional, Bernhardsson, Carolina, additional, Chatel, Stéphanie, additional, Karakachoff, Matilde, additional, Pierre, Aude Saint, additional, Herzig, Anthony F., additional, Olaso, Robert, additional, Monteil, Martial, additional, Gallien, Véronique, additional, Cabot, Elodie, additional, Svensson, Emma, additional, Bacq-Daian, Delphine, additional, Baron, Estelle, additional, Berthellier, Charlotte, additional, Besse, Céline, additional, Blanché, Hélène, additional, Bocher, Ozvan, additional, Boland, Anne, additional, Bonnaud, Stéphanie, additional, Charpentier, Eric, additional, Dandine-Roulland, Claire, additional, Férec, Claude, additional, Fruchet, Christine, additional, Lecointe, Simon, additional, Floch, Edith Le, additional, Ludwig, Thomas, additional, Marenne, Gaëlle, additional, Meyer, Vincent, additional, Quellery, Elisabeth, additional, Racimo, Fernando, additional, Rouault, Karen, additional, Sandron, Florian, additional, Schott, Jean-Jacques, additional, Suarez, Lourdes Velo, additional, Violleau, Jade, additional, Willerslev, Eske, additional, Coativy, Yves, additional, Jézéquel, Mael, additional, Le-Bris, Daniel, additional, Nicolas, Clément, additional, Pailler, Yvan, additional, Goldberg, Marcel, additional, Zins, Marie, additional, Le-Marec, Hervé, additional, Jakobsson, Mattias, additional, Darlu, Pierre, additional, Génin, Emmanuelle, additional, Deleuze, Jean-François, additional, Redon, Richard, additional, and Dina, Christian, additional

Published
2022
Full Text
View/download PDF

21. Testing the burden of rare variation in arrhythmia-susceptibility genes provides new insights into molecular diagnosis for Brugada syndrome

Author

Le Scouarnec, Solena, Karakachoff, Matilde, Gourraud, Jean-Baptiste, Lindenbaum, Pierre, Bonnaud, Stéphanie, Portero, Vincent, Duboscq-Bidot, Laëtitia, Daumy, Xavier, Simonet, Floriane, Teusan, Raluca, Baron, Estelle, Violleau, Jade, Persyn, Elodie, Bellanger, Lise, Barc, Julien, Chatel, Stéphanie, Martins, Raphaël, Mabo, Philippe, Sacher, Frédéric, Haïssaguerre, Michel, Kyndt, Florence, Schmitt, Sébastien, Bézieau, Stéphane, Le Marec, Hervé, Dina, Christian, Schott, Jean-Jacques, Probst, Vincent, and Redon, Richard

Published
2015
Full Text
View/download PDF

22. Genetic association analyses highlight IL6, ALPL, and NAV1 as three new susceptibility genes underlying calcific aortic valve stenosis

Author

Cohorte D.E.S.I.R., Gaudreault, Nathalie, Dina, Christian, Thériault, Sébastien, Messika-Zeitoun, David, Arsenault, Benoit, Le Scouarnec, Solena, Capoulade, Romain, Boureau, Anne-Sophie, Bossé, Yohan, Rigade, Sidwell, Lamontagne, Maxime, Li, Zhonglin, Pibarot, Philippe, Simonet, Floriane, Clavel, Marie-Annick, Dagenais, François, Mathieu, Patrick, Lecointe, Simon, Baron, Estelle, Bonnaud, Stéphanie, Karakachoff, Matilde, Charpentier, Eric, Fellah, Imen, Roussel, Jean-Christian, Verhoye, Jean Philippe, Baufreton, Christophe, Probst, Vincent, Roussel, Ronan, Redon, Richard, Le Tourneau, Thierry, Schott, Jean-Jacques, Cohorte D.E.S.I.R., Gaudreault, Nathalie, Dina, Christian, Thériault, Sébastien, Messika-Zeitoun, David, Arsenault, Benoit, Le Scouarnec, Solena, Capoulade, Romain, Boureau, Anne-Sophie, Bossé, Yohan, Rigade, Sidwell, Lamontagne, Maxime, Li, Zhonglin, Pibarot, Philippe, Simonet, Floriane, Clavel, Marie-Annick, Dagenais, François, Mathieu, Patrick, Lecointe, Simon, Baron, Estelle, Bonnaud, Stéphanie, Karakachoff, Matilde, Charpentier, Eric, Fellah, Imen, Roussel, Jean-Christian, Verhoye, Jean Philippe, Baufreton, Christophe, Probst, Vincent, Roussel, Ronan, Redon, Richard, Le Tourneau, Thierry, and Schott, Jean-Jacques

Abstract

Background: Calcific aortic valve stenosis (CAVS) is a frequent and life-threatening cardiovascular disease for which there is currently no medical treatment available. To date, only 2 genes, LPA and PALMD, have been identified as causal for CAVS. We aimed to identify additional susceptibility genes for CAVS. Methods: A GWAS (genome-wide association study) meta-analysis of 4 cohorts, totaling 5115 cases and 354 072 controls of European descent, was performed. A TWAS (transcriptome-wide association study) was completed to integrate transcriptomic data from 233 human aortic valves. A series of post-GWAS analyses were performed, including fine-mapping, colocalization, phenome-wide association studies, pathway, and tissue enrichment as well as genetic correlation with cardiovascular traits. Results: In the GWAS meta-analysis, 4 loci achieved genome-wide significance, including 2 new loci: IL6 (interleukin 6) on 7p15.3 and ALPL (alkaline phosphatase) on 1p36.12. A TWAS integrating gene expression from 233 human aortic valves identified NAV1 (neuron navigator 1) on 1q32.1 as a new candidate causal gene. The CAVS risk alleles were associated with higher mRNA expression of NAV1 in valve tissues. Fine-mapping identified rs1800795 as the most likely causal variant in the IL6 locus. The signal identified colocalizes with the expression of the IL6 RNA antisense in various tissues. Phenome-wide association analyses in the UK Biobank showed colocalized associations between the risk allele at the IL6 lead variant and higher eosinophil count, pulse pressure, systolic blood pressure, and carotid artery procedures, implicating modulation of the IL6 pathways. The risk allele at the NAV1 lead variant colocalized with higher pulse pressure and higher prevalence of carotid artery stenosis. Association results at the genome-wide scale indicated genetic correlation between CAVS, coronary artery disease, and cardiovascular risk factors. Conclusions: Our study implicates 3 new genetic loci i

Published
2020

28. Genetic association analyses highlight IL6, ALPL, and NAV1 as three new susceptibility genes underlying calcific aortic valve stenosis

Author

Cohorte D.E.S.I.R., Thériault, Sébastien, Dina, Christian, Messika-Zeitoun, David, Le Scouarnec, Solena, Capoulade, Romain, Gaudreault, Nathalie, Rigade, Sidwell, Li, Zhonglin, Simonet, Floriane, Lamontagne, Maxime, Clavel, Marie-Annick, Arsenault, Benoit, Boureau, Anne-Sophie, Lecointe, Simon, Baron, Estelle, Bonnaud, Stéphanie, Karakachoff, Matilde, Charpentier, Eric, Fellah, Imen, Roussel, Jean-Christian, Verhoye, Jean Philippe, Baufreton, Christophe, Probst, Vincent, Roussel, Ronan, Redon, Richard, Dagenais, François, Pibarot, Philippe, Mathieu, Patrick, Le Tourneau, Thierry, Bossé, Yohan, Schott, Jean-Jacques, Cohorte D.E.S.I.R., Thériault, Sébastien, Dina, Christian, Messika-Zeitoun, David, Le Scouarnec, Solena, Capoulade, Romain, Gaudreault, Nathalie, Rigade, Sidwell, Li, Zhonglin, Simonet, Floriane, Lamontagne, Maxime, Clavel, Marie-Annick, Arsenault, Benoit, Boureau, Anne-Sophie, Lecointe, Simon, Baron, Estelle, Bonnaud, Stéphanie, Karakachoff, Matilde, Charpentier, Eric, Fellah, Imen, Roussel, Jean-Christian, Verhoye, Jean Philippe, Baufreton, Christophe, Probst, Vincent, Roussel, Ronan, Redon, Richard, Dagenais, François, Pibarot, Philippe, Mathieu, Patrick, Le Tourneau, Thierry, Bossé, Yohan, and Schott, Jean-Jacques

Abstract

Background: Calcific aortic valve stenosis (CAVS) is a frequent and life-threatening cardiovascular disease for which there is currently no medical treatment available. To date, only 2 genes, LPA and PALMD, have been identified as causal for CAVS. We aimed to identify additional susceptibility genes for CAVS. Methods: A GWAS (genome-wide association study) meta-analysis of 4 cohorts, totaling 5115 cases and 354 072 controls of European descent, was performed. A TWAS (transcriptome-wide association study) was completed to integrate transcriptomic data from 233 human aortic valves. A series of post-GWAS analyses were performed, including fine-mapping, colocalization, phenome-wide association studies, pathway, and tissue enrichment as well as genetic correlation with cardiovascular traits. Results: In the GWAS meta-analysis, 4 loci achieved genome-wide significance, including 2 new loci: IL6 (interleukin 6) on 7p15.3 and ALPL (alkaline phosphatase) on 1p36.12. A TWAS integrating gene expression from 233 human aortic valves identified NAV1 (neuron navigator 1) on 1q32.1 as a new candidate causal gene. The CAVS risk alleles were associated with higher mRNA expression of NAV1 in valve tissues. Fine-mapping identified rs1800795 as the most likely causal variant in the IL6 locus. The signal identified colocalizes with the expression of the IL6 RNA antisense in various tissues. Phenome-wide association analyses in the UK Biobank showed colocalized associations between the risk allele at the IL6 lead variant and higher eosinophil count, pulse pressure, systolic blood pressure, and carotid artery procedures, implicating modulation of the IL6 pathways. The risk allele at the NAV1 lead variant colocalized with higher pulse pressure and higher prevalence of carotid artery stenosis. Association results at the genome-wide scale indicated genetic correlation between CAVS, coronary artery disease, and cardiovascular risk factors. Conclusions: Our study implicates 3 new genetic loci i

Published
2019

29. Genetic Association Analyses Highlight IL6 , ALPL , and NAV1 As 3 New Susceptibility Genes Underlying Calcific Aortic Valve Stenosis

Author

Thériault, Sébastien, primary, Dina, Christian, additional, Messika-Zeitoun, David, additional, Le Scouarnec, Solena, additional, Capoulade, Romain, additional, Gaudreault, Nathalie, additional, Rigade, Sidwell, additional, Li, Zhonglin, additional, Simonet, Floriane, additional, Lamontagne, Maxime, additional, Clavel, Marie-Annick, additional, Arsenault, Benoit J., additional, Boureau, Anne-Sophie, additional, Lecointe, Simon, additional, Baron, Estelle, additional, Bonnaud, Stéphanie, additional, Karakachoff, Matilde, additional, Charpentier, Eric, additional, Fellah, Imen, additional, Roussel, Jean-Christian, additional, Philippe Verhoye, Jean, additional, Baufreton, Christophe, additional, Probst, Vincent, additional, Roussel, Ronan, additional, Redon, Richard, additional, Dagenais, François, additional, Pibarot, Philippe, additional, Mathieu, Patrick, additional, Le Tourneau, Thierry, additional, Bossé, Yohan, additional, Schott, Jean-Jacques, additional, Balkau, B., additional, Ducimetière, P., additional, Eschwège, E., additional, Alhenc-Gelas, F., additional, Girault, A., additional, Fumeron, F., additional, Marre, M., additional, Bonnet, F., additional, Bonnefond, A., additional, Froguel, P., additional, Rancière, F., additional, Cogneau, J., additional, Born, C., additional, Caces, E., additional, Cailleau, M., additional, Lantieri, O, additional, Moreau, J.G., additional, Rakotozafy, F., additional, Tichet, J., additional, and Vol, S., additional

Published
2019
Full Text
View/download PDF

30. Dysfunction of the Voltage-Gated K + Channel b2 Subunit in a Familial Case of Brugada Syndrome

Author

Portero, Vincent, Le Scouarnec, Solena, Es-Salah-Lamoureux, Zeineb, Burel, Sophie, Gourraud, Jean-Baptiste, Bonnaud, Stephanie, Lindenbaum, Pierre, Simonet, Floriane, Violleau, Jade, Baron, Estelle, Moreau, Eleonore, Scott, Carol, Chatel, Stephanie, Loussouarn, Gildas, O 'hara, Thomas, Mabo, Philippe, Dina, Christian, Le Marec, Herve, Schott, Jean-Jacques, Probst, Vincent, Baro, Isabelle, Marionneau, Céline, Charpentier, Flavien, Redon, Richard, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), The Wellcome Trust Sanger Institute [Cambridge], Johns Hopkins University (JHU), Service de cardiologie et maladies vasculaires, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]

Subjects
[SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, cardiovascular diseases
Abstract

International audience; Background - The Brugada syndrome is an inherited cardiac arrhythmia associated with high risk of sudden death. Although 20% of patients with Brugada syndrome carry mutations in SCN5A, the molecular mechanisms underlying this condition are still largely unknown.Methods and Results - We combined whole‐exome sequencing and linkage analysis to identify the genetic variant likely causing Brugada syndrome in a pedigree for which SCN5A mutations had been excluded. This approach identified 6 genetic variants cosegregating with the Brugada electrocardiographic pattern within the pedigree. In silico gene prioritization pointed to 1 variant residing in KCNAB2, which encodes the voltage‐gated K+ channel β2‐subunit (Kvβ2‐R12Q). Kvβ2 is widely expressed in the human heart and has been shown to interact with the fast transient outward K+ channel subunit Kv4.3, increasing its current density. By targeted sequencing of the KCNAB2 gene in 167 unrelated patients with Brugada syndrome, we found 2 additional rare missense variants (L13F and V114I). We then investigated the physiological effects of the 3 KCNAB2 variants by using cellular electrophysiology and biochemistry. Patch‐clamp experiments performed in COS‐7 cells expressing both Kv4.3 and Kvβ2 revealed a significant increase in the current density in presence of the R12Q and L13F Kvβ2 mutants. Although biotinylation assays showed no differences in the expression of Kv4.3, the total and submembrane expression of Kvβ2‐R12Q were significantly increased in comparison with wild‐type Kvβ2.Conclusions - Altogether, our results indicate that Kvβ2 dysfunction can contribute to the Brugada electrocardiographic pattern.

Published
2016

31. Genetic Association Analyses Highlight IL6, ALPL, and NAV1 As 3 New Susceptibility Genes Underlying Calcific Aortic Valve Stenosis.

Author

Thériault, Sébastien, Dina, Christian, Messika-Zeitoun, David, Le Scouarnec, Solena, Capoulade, Romain, Gaudreault, Nathalie, Rigade, Sidwell, Li, Zhonglin, Simonet, Floriane, Lamontagne, Maxime, Clavel, Marie-Annick, Arsenault, Benoit J., Boureau, Anne-Sophie, Lecointe, Simon, Baron, Estelle, Bonnaud, Stéphanie, Karakachoff, Matilde, Charpentier, Eric, Fellah, Imen, and Roussel, Jean-Christian

Abstract

Supplemental Digital Content is available in the text. Background: Calcific aortic valve stenosis (CAVS) is a frequent and life-threatening cardiovascular disease for which there is currently no medical treatment available. To date, only 2 genes, LPA and PALMD , have been identified as causal for CAVS. We aimed to identify additional susceptibility genes for CAVS. Methods: A GWAS (genome-wide association study) meta-analysis of 4 cohorts, totaling 5115 cases and 354 072 controls of European descent, was performed. A TWAS (transcriptome-wide association study) was completed to integrate transcriptomic data from 233 human aortic valves. A series of post-GWAS analyses were performed, including fine-mapping, colocalization, phenome-wide association studies, pathway, and tissue enrichment as well as genetic correlation with cardiovascular traits. Results: In the GWAS meta-analysis, 4 loci achieved genome-wide significance, including 2 new loci: IL6 (interleukin 6) on 7p15.3 and ALPL (alkaline phosphatase) on 1p36.12. A TWAS integrating gene expression from 233 human aortic valves identified NAV1 (neuron navigator 1) on 1q32.1 as a new candidate causal gene. The CAVS risk alleles were associated with higher mRNA expression of NAV1 in valve tissues. Fine-mapping identified rs1800795 as the most likely causal variant in the IL6 locus. The signal identified colocalizes with the expression of the IL6 RNA antisense in various tissues. Phenome-wide association analyses in the UK Biobank showed colocalized associations between the risk allele at the IL6 lead variant and higher eosinophil count, pulse pressure, systolic blood pressure, and carotid artery procedures, implicating modulation of the IL6 pathways. The risk allele at the NAV1 lead variant colocalized with higher pulse pressure and higher prevalence of carotid artery stenosis. Association results at the genome-wide scale indicated genetic correlation between CAVS, coronary artery disease, and cardiovascular risk factors. Conclusions: Our study implicates 3 new genetic loci in CAVS pathogenesis, which constitute novel targets for the development of therapeutic agents. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

32. Dysfunction of the Voltage‐Gated K + Channel β2 Subunit in a Familial Case of Brugada Syndrome

Author

Portero, Vincent, primary, Le Scouarnec, Solena, additional, Es‐Salah‐Lamoureux, Zeineb, additional, Burel, Sophie, additional, Gourraud, Jean‐Baptiste, additional, Bonnaud, Stéphanie, additional, Lindenbaum, Pierre, additional, Simonet, Floriane, additional, Violleau, Jade, additional, Baron, Estelle, additional, Moreau, Eléonore, additional, Scott, Carol, additional, Chatel, Stéphanie, additional, Loussouarn, Gildas, additional, O'Hara, Thomas, additional, Mabo, Philippe, additional, Dina, Christian, additional, Le Marec, Hervé, additional, Schott, Jean‐Jacques, additional, Probst, Vincent, additional, Baró, Isabelle, additional, Marionneau, Céline, additional, Charpentier, Flavien, additional, and Redon, Richard, additional

Published
2016
Full Text
View/download PDF

33. Variants of Transient Receptor Potential Melastatin Member 4 in Childhood Atrioventricular Block

Author

Syam, Ninda, primary, Chatel, Stéphanie, additional, Ozhathil, Lijo Cherian, additional, Sottas, Valentin, additional, Rougier, Jean‐Sébastien, additional, Baruteau, Alban, additional, Baron, Estelle, additional, Amarouch, Mohamed‐Yassine, additional, Daumy, Xavier, additional, Probst, Vincent, additional, Schott, Jean‐Jacques, additional, and Abriel, Hugues, additional

Published
2016
Full Text
View/download PDF

34. Genetic Association Analyses Highlight IL6, ALPL, and NAV1As 3 New Susceptibility Genes Underlying Calcific Aortic Valve Stenosis

Author

Thériault, Sébastien, Dina, Christian, Messika-Zeitoun, David, Le Scouarnec, Solena, Capoulade, Romain, Gaudreault, Nathalie, Rigade, Sidwell, Li, Zhonglin, Simonet, Floriane, Lamontagne, Maxime, Clavel, Marie-Annick, Arsenault, Benoit J., Boureau, Anne-Sophie, Lecointe, Simon, Baron, Estelle, Bonnaud, Stéphanie, Karakachoff, Matilde, Charpentier, Eric, Fellah, Imen, Roussel, Jean-Christian, Philippe Verhoye, Jean, Baufreton, Christophe, Probst, Vincent, Roussel, Ronan, Redon, Richard, Dagenais, François, Pibarot, Philippe, Mathieu, Patrick, Le Tourneau, Thierry, Bossé, Yohan, Schott, Jean-Jacques, Balkau, B., Ducimetière, P., Eschwège, E., Alhenc-Gelas, F., Girault, A., Fumeron, F., Marre, M., Bonnet, F., Bonnefond, A., Froguel, P., Rancière, F., Cogneau, J., Born, C., Caces, E., Cailleau, M., Lantieri, O, Moreau, J.G., Rakotozafy, F., Tichet, J., and Vol, S.

Abstract

Supplemental Digital Content is available in the text.

Published
2019
Full Text
View/download PDF

35. Multifocal Ectopic Purkinje-Related Premature Contractions: A New SCN5A-Related Cardiac Channelopathy

Author

Laurent, Gabriel, Saal, Samuel, Amarouch, Mohamed Yassine, Béziau, Delphine, Marsman, Roos, Faivre, Laurence, Barc, Julien, Dina, Christian, Bertaux, Geraldine, Barthez, Olivier, Thauvin-Robinet, Christel, Charron, Philippe, Fressart, Véronique, Maltret, Alice, Villain, Elisabeth, Baron, Estelle, Mérot, Jean, Turpault, Rodolphe, Coudière, Yves, Charpentier, Flavien, Schott, Jean-Jacques, Loussouarn, Gildas, Wilde, Arthur, Wolf, Jean-Eric, Baró, Isabelle, Kyndt, Florence, Probst, Vincent, Service de Cardiologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Experimental Cardiology, Heart Failure Research Center (HFRC)-Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Génétique, pharmacologie et physiopathologie des maladies cardiovasculaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Fonctionnelle de Cardiogénétique et Myogénétique Moléculaire et Cellulaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Mathématiques Jean Leray (LMJL), Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN), The Agence Nationale de la Recherche financially supported R.T. and Y.C. (ANR-07-JCJC-0141), I.B. (ANR-09-GENO-003-01) and J.-J.S. (ANR-05- MRAR-028-01). J.-J.S. was also supported by a Leducq Foundation Trans-Atlantic Network of Excellence grant (05 CVD 01). The research leading to these results has also received funding from the European Community's Seventh Framework Programme FP7/ 2007-2013 under grant agreement n° FP7-HEALTH-2009-singlestage 241526 (I.B. and F.C.). G.Lo. was financially supported by the Association Française contre les Myopathies (n°14120) and F.C. by the Fondation pour la Recherche Médicale (DVC20070409253)., Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), unité de recherche de l'institut du thorax UMR1087 UMR6291 ( ITX ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Heart Failure Research Center (HFRC)-Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Centre de Génétique Moléculaire et Chromosomique du GH Pitié-Salpêtrière-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Laboratoire de Mathématiques Jean Leray ( LMJL ), Université de Nantes ( UN ) -Centre National de la Recherche Scientifique ( CNRS ), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Heart Failure Research Center (HFRC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), and Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, cardiovascular system, cardiovascular diseases, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract

International audience; OBJECTIVES: The aim of this study was to describe a new familial cardiac phenotype and to elucidate the electrophysiological mechanism responsible for the disease. BACKGROUND: Mutations in several genes encoding ion channels, especially SCN5A, have emerged as the basis for a variety of inherited cardiac arrhythmias. METHODS: Three unrelated families comprising 21 individuals affected by multifocal ectopic Purkinje-related premature contractions (MEPPC) characterized by narrow junctional and rare sinus beats competing with numerous premature ventricular contractions with right and/or left bundle branch block patterns were identified. RESULTS: Dilated cardiomyopathy was identified in 6 patients, atrial arrhythmias were detected in 9 patients, and sudden death was reported in 5 individuals. Invasive electrophysiological studies demonstrated that premature ventricular complexes originated from the Purkinje tissue. Hydroquinidine treatment dramatically decreased the number of premature ventricular complexes. It normalized the contractile function in 2 patients. All the affected subjects carried the c.665G>A transition in the SCN5A gene. Patch-clamp studies of resulting p.Arg222Gln (R222Q) Nav1.5 revealed a net gain of function of the sodium channel, leading, in silico, to incomplete repolarization in Purkinje cells responsible for premature ventricular action potentials. In vitro and in silico studies recapitulated the normalization of the ventricular action potentials in the presence of quinidine. CONCLUSIONS: A new SCN5A-related cardiac syndrome, MEPPC, was identified. The SCN5A mutation leads to a gain of function of the sodium channel responsible for hyperexcitability of the fascicular-Purkinje system. The MEPPC syndrome is responsive to hydroquinidine.

Published
2012

36. Multifocal ectopic Purkinje-related premature contractions: a new SCN5A-related cardiac channelopathy

Author

Laurent, Gabriel, Saal, Samuel, Amarouch, Mohamed Yassine, Béziau, Delphine M., Marsman, Roos F.J., Faivre, Laurence, Barc, Julien, Dina, Christian, Bertaux, Geraldine, Barthez, Olivier, Thauvin-Robinet, Christel, Charron, Philippe, Fressart, Véronique, Maltret, Alice, Villain, Elisabeth, Baron, Estelle, Mérot, Jean, Turpault, Rodolphe, Coudière, Yves, Charpentier, Flavien, Schott, Jean-Jacques, Loussouarn, Gildas, Wilde, Arthur A.M., Wolf, Jean-Eric, Baró, Isabelle, Kyndt, Florence, Probst, Vincent, Cardiology, Medical Biology, and ACS - Amsterdam Cardiovascular Sciences

Subjects
Adult, Cardiomyopathy, Dilated, Male, Patch-Clamp Techniques, Adolescent, DNA Mutational Analysis, arrhythmia, Sodium Channels, NAV1.5 Voltage-Gated Sodium Channel, Purkinje Fibers, Young Adult, Humans, cardiovascular diseases, Child, SCN5A, Genetic Association Studies, Infant, Newborn, Infant, Arrhythmias, Cardiac, Syndrome, Middle Aged, Myocardial Contraction, Quinidine, Ventricular Premature Complexes, Pedigree, Death, Sudden, Cardiac, Phenotype, Mutation, cardiovascular system, Female, ventricular tachycardia, Electrophysiologic Techniques, Cardiac, Anti-Arrhythmia Agents
Abstract

Objectives The aim of this study was to describe a new familial cardiac phenotype and to elucidate the electrophysiological mechanism responsible for the disease. Background Mutations in several genes encoding ion channels, especially SCN5A, have emerged as the basis for a variety of inherited cardiac arrhythmias. Methods Three unrelated families comprising 21 individuals affected by multifocal ectopic Purkinje-related premature contractions (MEPPC) characterized by narrow junctional and rare sinus beats competing with numerous premature ventricular contractions with right and/or left bundle branch block patterns were identified. Results Dilated cardiomyopathy was identified in 6 patients, atrial arrhythmias were detected in 9 patients, and sudden death was reported in 5 individuals. Invasive electrophysiological studies demonstrated that premature ventricular complexes originated from the Purkinje tissue. Hydroquinidine treatment dramatically decreased the number of premature ventricular complexes. It normalized the contractile function in 2 patients. All the affected subjects carried the c.665G>A transition in the SCN5A gene. Patch-clamp studies of resulting p.Arg222Gln (R222Q) Nav1.5 revealed a net gain of function of the sodium channel, leading, in silico, to incomplete repolarization in Purkinje cells responsible for premature ventricular action potentials. In vitro and in silico studies recapitulated the normalization of the ventricular action potentials in the presence of quinidine. Conclusions A new SCN5A-related cardiac syndrome, MEPPC, was identified. The SCN5A mutation leads to a gain of function of the sodium channel responsible for hyperexcitability of the fascicular-Purkinje system. The MEPPC syndrome is responsive to hydroquinidine. (J Am Coll Cardiol 2012;60:144-56) (C) 2012 by the American College of Cardiology Foundation

Published
2011

37. 0185 : Genetic screening identifies a high proportion of mutations in patients with idiopathic ventricular fibrillation and sudden cardiac death

Author

Probst, Vincent, primary, Le Scouarnec, Solena, additional, Kyndt, Florence, additional, Schott, Jean-Jacques, additional, Gourraud, Jean-Baptiste, additional, Sacher, Frederic, additional, Mabo, Philippe, additional, Karakachoff, Matilde, additional, Bonnaud, Stéphanie, additional, Violleau, Jade, additional, Marijon, Eloi, additional, Dumas, Florence, additional, Cariou, Alain, additional, Baron, Estelle, additional, Lindenbaum, Pierre, additional, Jouven, Xavier, additional, and Redon, Richard, additional

Published
2015
Full Text
View/download PDF

38. A Connexin40 Mutation Associated With a Malignant Variant of Progressive Familial Heart Block Type I

Author

Makita, Naomasa, Seki, Akiko, Sumitomo, Naokata, Chkourko, Halina, Fukuhara, Shigetomo, Watanabe, Hiroshi, Shimizu, Wataru, Bezzina, Connie R., Hasdemir, Can, Mugishima, Hideo, Makiyama, Takeru, Baruteau, Alban, Baron, Estelle, Horie, Minoru, Hagiwara, Nobuhisa, Wilde, Arthur A.M., Probst, Vincent, Le, Marec Hervé, Roden, Dan M., Mochizuki, Naoki, Schott, Jean-Jacques, Delmar, Mario, Makita, Naomasa, Seki, Akiko, Sumitomo, Naokata, Chkourko, Halina, Fukuhara, Shigetomo, Watanabe, Hiroshi, Shimizu, Wataru, Bezzina, Connie R., Hasdemir, Can, Mugishima, Hideo, Makiyama, Takeru, Baruteau, Alban, Baron, Estelle, Horie, Minoru, Hagiwara, Nobuhisa, Wilde, Arthur A.M., Probst, Vincent, Le, Marec Hervé, Roden, Dan M., Mochizuki, Naoki, Schott, Jean-Jacques, and Delmar, Mario

Abstract

Background-Progressive familial heart block type I (PFHBI) is a hereditary arrhythmia characterized by progressive conduction disturbances in the His-Purkinje system. PFHBI has been linked to genes such as SCN5A that influence cardiac excitability but not to genes that influence cell-to-cell communication. Our goal was to explore whether nucleotide substitutions in genes coding for connexin proteins would associate with clinical cases of PFHBI and if so, to establish a genotype-cell phenotype correlation for that mutation. Methods and Results-We screened 156 probands with PFHBI. In addition to 12 sodium channel mutations, we found a germ line GJA5 (connexin40 [Cx40]) mutation (Q58L) in 1 family. Heterologous expression of Cx40-Q58L in connexin-deficient neuroblastoma cells resulted in marked reduction of junctional conductance (Cx40-wild type [WT], 22.2 ± 1.7 nS, n=14; Cx40-Q58L, 0.56 ± 0.34 nS, n=14; P <0.001) and diffuse localization of immunoreactive proteins in the vicinity of the plasma membrane without formation of gap junctions. Heteromeric cotransfection of Cx40-WT and Cx40-Q58L resulted in homogenous distribution of proteins in the plasma membrane rather than in membrane plaques in ̃ 50% of cells; well-defined gap junctions were observed in other cells. Junctional conductance values correlated with the distribution of gap junction plaques. Conclusions-Mutation Cx40-Q58L impairs gap junction formation at cell-cell interfaces. This is the first demonstration of a germ line mutation in a connexin gene that associates with inherited ventricular arrhythmias and emphasizes the importance of Cx40 in normal propagation in the specialized conduction system., Circulation: Arrhythmia and Electrophysiology, 5(1), pp.163-172; 2012

Published
2012

39. A Connexin40 Mutation Associated With a Malignant Variant of Progressive Familial Heart Block Type I

Author

Makita, Naomasa, primary, Seki, Akiko, additional, Sumitomo, Naokata, additional, Chkourko, Halina, additional, Fukuhara, Shigetomo, additional, Watanabe, Hiroshi, additional, Shimizu, Wataru, additional, Bezzina, Connie R., additional, Hasdemir, Can, additional, Mugishima, Hideo, additional, Makiyama, Takeru, additional, Baruteau, Alban, additional, Baron, Estelle, additional, Horie, Minoru, additional, Hagiwara, Nobuhisa, additional, Wilde, Arthur A.M., additional, Probst, Vincent, additional, Le Marec, Hervé, additional, Roden, Dan M., additional, Mochizuki, Naoki, additional, Schott, Jean-Jacques, additional, and Delmar, Mario, additional

Published
2012
Full Text
View/download PDF

40. Screening for Copy Number Variation in Genes Associated With the Long QT Syndrome

Author

Barc, Julien, primary, Briec, François, additional, Schmitt, Sébastien, additional, Kyndt, Florence, additional, Le Cunff, Martine, additional, Baron, Estelle, additional, Vieyres, Claude, additional, Sacher, Frédéric, additional, Redon, Richard, additional, Le Caignec, Cédric, additional, Le Marec, Hervé, additional, Probst, Vincent, additional, and Schott, Jean-Jacques, additional

Published
2011
Full Text
View/download PDF

41. Screening for Copy Number Variation in Genes Associated With the Long QT Syndrome Clinical Relevance

Author

Barc, Julien, Briec, François, Schmitt, Sébastien, Kyndt, Florence, Le Cunff, Martine, Baron, Estelle, Vieyres, Claude, Sacher, Frédéric, Redon, Richard, Le Caignec, Cédric, Le Marec, Hervé, Probst, Vincent, and Schott, Jean-Jacques

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, CNV, long QT syndrome, sudden death, cardiovascular diseases, deletion, MLPA
Abstract

ObjectivesThe aim of this study was to investigate, in a set of 93 mutation-negative long QT syndrome (LQTS) probands, the frequency of copy number variants (CNVs) in LQTS genes.BackgroundLQTS is an inherited cardiac arrhythmia characterized by a prolonged heart rate–corrected QT (QTc) interval associated with sudden cardiac death. Recent studies suggested the involvement of duplications or deletions in the occurrence of LQTS. However, their frequency remains unknown in LQTS patients.MethodsPoint mutations in KCNQ1, KCNH2, and SCN5A genes were excluded by denaturing high-performance liquid chromatography or direct sequencing. We applied Multiplex Ligation-dependent Probe Amplification (MLPA) to detect CNVs in exons of these 3 genes. Abnormal exon copy numbers were confirmed by quantitative multiplex PCR of short fluorescent fragment (QMPSF). Array-based comparative genomic hybridization (array CGH) analysis was performed using Agilent Human Genome 244K Microarrays to further map the genomic rearrangements.ResultsWe identified 3 different deletions in 3 unrelated families: 1 in KCNQ1 and 2 involving KCNH2. We showed in the largest family that the deletion involving KCNH2 is fully penetrant and segregates with the long QT phenotype in 7 affected members.ConclusionsOur study demonstrates that CNVs in KCNQ1 and KCNH2 explain around 3% of LQTS in patients with no point mutation in these genes. This percentage is likely higher than the frequency of point mutations in ANKB, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP9, and SNTA1 together. Thus, we propose that CNV screening in KCNQ1 and KCNH2 may be performed routinely in LQTS patients.

Full Text
View/download PDF

42. Targeted resequencing identifies TRPM4 as a major gene predisposing to progressive familial heart block type I

Author

Bianchi, Beatrice, Barc, Julien, Schott, Jean-Jacques, Abriel, Hugues, Makita, Naomasa, Bonnaud, Stéphanie, Probst, Vincent, Dina, Christian, Redon, Richard, Thollet, Aurélie, Nafzger, Sabine Naomi, Lindenbaum, Pierre, Charpentier, Eric, Le Scouarnec, Solena, Fouchard, Swanny, Kyndt, Florence, Le Marec, Hervé, Gourraud, Jean-Baptiste, Baron, Estelle, Amarouch, Mohamed Yassine, and Daumy, Xavier

Subjects
610 Medicine & health, 3. Good health
Abstract

BACKGROUND Progressive cardiac conduction disease (PCCD) is one of the most common cardiac conduction disturbances. It has been causally related to rare mutations in several genes including SCN5A, SCN1B, TRPM4, LMNA and GJA5. METHODS AND RESULTS In this study, by applying targeted next-generation sequencing (NGS) in 95 unrelated patients with PCCD, we have identified 13 rare variants in the TRPM4 gene, two of which are currently absent from public databases. This gene encodes a cardiac calcium-activated cationic channel which precise role and importance in cardiac conduction and disease is still debated. One novel variant, TRPM4-p.I376T, is carried by the proband of a large French 4-generation pedigree. Systematic familial screening showed that a total of 13 family members carry the mutation, including 10 out of the 11 tested affected individuals versus only 1 out of the 21 unaffected ones. Functional and biochemical analyses were performed using HEK293 cells, in whole-cell patch-clamp configuration and Western blotting. TRPM4-p.I376T results in an increased current density concomitant to an augmented TRPM4 channel expression at the cell surface. CONCLUSIONS This study is the first extensive NGS-based screening of TRPM4 coding variants in patients with PCCD. It reports the third largest pedigree diagnosed with isolated Progressive Familial Heart Block type I and confirms that this subtype of PCCD is caused by mutation-induced gain-of-expression and function of the TRPM4 ion channel.

43. Multifocal Ectopic Purkinje Tachycardia: A New Familial Syndrome

Author

Laurent, Gabriel, Saal, Samuel, Amarouch, Mohamed Yassine, Faivre, Laurence, Thauvin-Robinet, Christel, Charron, Philippe, Richard, Pascale, Probst, Vincent, Baron, Estelle, Baro, Isabelle, julien barc, Schott, Jean Jacques, Merot, Jean, Turpault, Rodolphe, Coudiere, Yves, Loussouam, Gildas, Kyndt, Florence, and Wolf, Jean Eric

44. Dysfunction of the Voltage-Gated K+ Channel β2 Subunit in a Familial Case of Brugada Syndrome.

Author

Portero, Vincent, Le Scouarnec, Solena, Es ‐ Salah ‐ Lamoureux, Zeineb, Burel, Sophie, Gourraud, Jean ‐ Baptiste, Bonnaud, Stéphanie, Lindenbaum, Pierre, Simonet, Floriane, Violleau, Jade, Baron, Estelle, Moreau, Eléonore, Scott, Carol, Chatel, Stéphanie, Loussouarn, Gildas, O'Hara, Thomas, Mabo, Philippe, Dina, Christian, Le Marec, Hervé, Schott, Jean ‐ Jacques, and Probst, Vincent

Published
2016
Full Text
View/download PDF

45. New Equipment for Measurement of Soiling and Specular Reflectance on Solar Mirrors

Author

Angela Disdier, Estelle Le Baron, Frédéric Vidal, Antoine Grosjean, Delphine Bourdon, Anne-Claire Pescheux, Département Technique Conversion et Hydrogène (DTCH), Laboratoire d'Innovation pour les Technologies des Energies Nouvelles et les nanomatériaux (LITEN), Institut National de L'Energie Solaire (INES), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de L'Energie Solaire (INES), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Procédés, Matériaux et Energie Solaire (PROMES), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physico-chimie des Polymères et des Interfaces (LPPI), Fédération INSTITUT DES MATÉRIAUX DE CERGY-PONTOISE (I-MAT), Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine, Européen grant agreement No. 654479, European Project: 654479,H2020,H2020-LCE-2015-1-two-stage,WASCOP(2016), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de L'Energie Solaire (INES), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), LE BARON, Estelle, and Water Saving for Solar Concentrated Power - WASCOP - - H20202016-01-01 - 2019-12-31 - 654479 - VALID

Subjects
business.industry, 020209 energy, Life time, 02 engineering and technology, [SPI.MAT] Engineering Sciences [physics]/Materials, 021001 nanoscience & nanotechnology, 7. Clean energy, Solar mirror, Reflective layer, Photodiode, law.invention, Abrasion (geology), [SPI.MAT]Engineering Sciences [physics]/Materials, Wavelength, Optics, law, Concentrated solar power, 0202 electrical engineering, electronic engineering, information engineering, Environmental science, Specular reflection, 0210 nano-technology, business
Abstract

International audience; During the life time of Concentrated Solar Power (CSP) plants, optical performance of solar mirrors is affected by soiling phenomena and surface degradation. It is imperative to dissociate soiling that requires cleaning from irreversible degradations which affect the plant performance. In both cases, small degradations or dust deposition cause an optical reflectance loss. In order to provide an adequate cleaning strategy, operators need to determine soiling-induced performance loss. Several commercial instruments already exist to measure optical reflectance, but they are dedicated to a single wavelength range or angle, punctual measurements or to laboratory analyses. CEA has developed a new kind of laboratory sensor to measure separately the loss of reflectance due to the degradation and soiling, thanks to a CCD camera and photodiodes. This equipment allows addressing variable wavelength, incidence and acceptance angles, to compare specular and hemispherical reflectance from other devices. The analysis of the images will quantify the soiling rate in order to optimize the frequency of cleaning water operations. The aim of the present contribution is to distinguish soiling from degradations (abrasion or corrosion of the reflective layer). This paper reviews the different current research works on prototype instruments and a comparison of this new alternative instrument with available commercial ones.

Published
2019

46. Letters.

Author

Crabtree, Linda, Juede, A. Herbert, Beckley, Brenda, Ball, Orville, Ballou, Laurel, Leroy, Elton, Davey, Nancy, Cascio, John, Linder, Marc, Kildahl, John, Bull, Silas Left Hand, Baron, Estelle, Schreiber, Denny L., Barkley, Judy, Rothlaui, D. M., Keltz, Pauline H., and Kyler, Jim

Subjects
*LETTERS to the editor, *INTERNATIONAL visitors, *POPULATION, *TRIALS (Law)
Abstract

Presents several letters to the editor. Comment on the strong population of foreigners in Southern California; Comment on the article "Will the West Take Over?," published in one of the previous issues of the journal "The Saturday Evening Post"; Appreciation of T.S. Matthews' article "The Meaning of the Eichmann Trial," published in the June 10 issue of the journal.

Published
1961

47. Multifocal ectopic Purkinje-related premature contractions: a new SCN5A-related cardiac channelopathy.

Author

Laurent G, Saal S, Amarouch MY, Béziau DM, Marsman RF, Faivre L, Barc J, Dina C, Bertaux G, Barthez O, Thauvin-Robinet C, Charron P, Fressart V, Maltret A, Villain E, Baron E, Mérot J, Turpault R, Coudière Y, Charpentier F, Schott JJ, Loussouarn G, Wilde AA, Wolf JE, Baró I, Kyndt F, and Probst V

Subjects
Adolescent, Adult, Anti-Arrhythmia Agents therapeutic use, Arrhythmias, Cardiac genetics, Cardiomyopathy, Dilated genetics, Child, DNA Mutational Analysis, Death, Sudden, Cardiac, Electrophysiologic Techniques, Cardiac, Female, Genetic Association Studies, Humans, Infant, Infant, Newborn, Male, Middle Aged, Mutation, Myocardial Contraction drug effects, Myocardial Contraction genetics, NAV1.5 Voltage-Gated Sodium Channel, Patch-Clamp Techniques, Pedigree, Phenotype, Quinidine analogs & derivatives, Quinidine therapeutic use, Sodium Channels physiology, Syndrome, Ventricular Premature Complexes drug therapy, Ventricular Premature Complexes physiopathology, Young Adult, Purkinje Fibers physiopathology, Sodium Channels genetics, Ventricular Premature Complexes genetics
Abstract

Objectives: The aim of this study was to describe a new familial cardiac phenotype and to elucidate the electrophysiological mechanism responsible for the disease., Background: Mutations in several genes encoding ion channels, especially SCN5A, have emerged as the basis for a variety of inherited cardiac arrhythmias., Methods: Three unrelated families comprising 21 individuals affected by multifocal ectopic Purkinje-related premature contractions (MEPPC) characterized by narrow junctional and rare sinus beats competing with numerous premature ventricular contractions with right and/or left bundle branch block patterns were identified., Results: Dilated cardiomyopathy was identified in 6 patients, atrial arrhythmias were detected in 9 patients, and sudden death was reported in 5 individuals. Invasive electrophysiological studies demonstrated that premature ventricular complexes originated from the Purkinje tissue. Hydroquinidine treatment dramatically decreased the number of premature ventricular complexes. It normalized the contractile function in 2 patients. All the affected subjects carried the c.665G>A transition in the SCN5A gene. Patch-clamp studies of resulting p.Arg222Gln (R222Q) Nav1.5 revealed a net gain of function of the sodium channel, leading, in silico, to incomplete repolarization in Purkinje cells responsible for premature ventricular action potentials. In vitro and in silico studies recapitulated the normalization of the ventricular action potentials in the presence of quinidine., Conclusions: A new SCN5A-related cardiac syndrome, MEPPC, was identified. The SCN5A mutation leads to a gain of function of the sodium channel responsible for hyperexcitability of the fascicular-Purkinje system. The MEPPC syndrome is responsive to hydroquinidine., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Published
2012
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results