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3. Transethnic genome-wide association study provides insights in the genetic architecture and heritability of long QT syndrome

Author

Lahrouchi, N, Tadros, R, Crotti, L, Mizusawa, Y, Postema, P, Beekman, L, Walsh, R, Hasegawa, K, Barc, J, Ernsting, M, Turkowski, K, Mazzanti, A, Beckmann, B, Shimamoto, K, Diamant, U, Wijeyeratne, Y, Kucho, Y, Robyns, T, Ishikawa, T, Arbelo, E, Christiansen, M, Winbo, A, Jabbari, R, Lubitz, S, Steinfurt, J, Rudic, B, Loeys, B, Shoemaker, M, Weeke, P, Pfeiffer, R, Davies, B, Andorin, A, Hofman, N, Dagradi, F, Pedrazzini, M, Tester, D, Bos, J, Sarquella-Brugada, G, Campuzano, Ó, Platonov, P, Stallmeyer, B, Zumhagen, S, Nannenberg, E, Veldink, J, van den Berg, L, Al-Chalabi, A, Shaw, C, Shaw, P, Morrison, K, Andersen, P, Müller-Nurasyid, M, Cusi, D, Barlassina, C, Galan, P, Lathrop, M, Munter, M, Werge, T, Ribasés, M, Aung, T, Khor, C, Ozaki, M, Lichtner, P, Meitinger, T, van Tintelen, J, Hoedemaekers, Y, Denjoy, I, Leenhardt, A, Napolitano, C, Shimizu, W, Schott, J, Gourraud, J, Makiyama, T, Ohno, S, Itoh, H, Krahn, A, Antzelevitch, C, Roden, D, Saenen, J, Borggrefe, M, Odening, K, Ellinor, P, Tfelt-Hansen, J, Skinner, J, van den Berg, M, Olesen, M, Brugada, J, Brugada, R, Makita, N, Breckpot, J, Yoshinaga, M, Behr, E, Rydberg, A, Aiba, T, Kääb, S, Priori, S, Guicheney, P, Tan, H, Newton-Cheh, C, Ackerman, M, Schwartz, P, Schulze-Bahr, E, Probst, V, Horie, M, Wilde, A, Tanck, M, Bezzina, C, Lahrouchi N, Tadros R, Crotti L, Mizusawa Y, Postema PG, Beekman L, Walsh R, Hasegawa K, Barc J, Ernsting M, Turkowski KL, Mazzanti A, Beckmann BM, Shimamoto K, Diamant UB, Wijeyeratne YD, Kucho Y, Robyns T, Ishikawa T, Arbelo E, Christiansen M, Winbo A, Jabbari R, Lubitz SA, Steinfurt J, Rudic B, Loeys B, Shoemaker MB, Weeke PE, Pfeiffer R, Davies B, Andorin A, Hofman N, Dagradi F, Pedrazzini M, Tester DJ, Bos JM, Sarquella-Brugada G, Campuzano Ó, Platonov PG, Stallmeyer B, Zumhagen S, Nannenberg EA, Veldink JH, van den Berg LH, Al-Chalabi A, Shaw CE, Shaw PJ, Morrison KE, Andersen PM, Müller-Nurasyid M, Cusi D, Barlassina C, Galan P, Lathrop M, Munter M, Werge T, Ribasés M, Aung T, Khor CC, Ozaki M, Lichtner P, Meitinger T, van Tintelen JP, Hoedemaekers Y, Denjoy I, Leenhardt A, Napolitano C, Shimizu W, Schott JJ, Gourraud JB, Makiyama T, Ohno S, Itoh H, Krahn AD, Antzelevitch C, Roden DM, Saenen J, Borggrefe M, Odening KE, Ellinor PT, Tfelt-Hansen J, Skinner JR, van den Berg MP, Olesen MS, Brugada J, Brugada R, Makita N, Breckpot J, Yoshinaga M, Behr ER, Rydberg A, Aiba T, Kääb S, Priori SG, Guicheney P, Tan HL, Newton-Cheh C, Ackerman MJ, Schwartz PJ, Schulze-Bahr E, Probst V, Horie M, Wilde AA, Tanck MWT, Bezzina CR., Lahrouchi, N, Tadros, R, Crotti, L, Mizusawa, Y, Postema, P, Beekman, L, Walsh, R, Hasegawa, K, Barc, J, Ernsting, M, Turkowski, K, Mazzanti, A, Beckmann, B, Shimamoto, K, Diamant, U, Wijeyeratne, Y, Kucho, Y, Robyns, T, Ishikawa, T, Arbelo, E, Christiansen, M, Winbo, A, Jabbari, R, Lubitz, S, Steinfurt, J, Rudic, B, Loeys, B, Shoemaker, M, Weeke, P, Pfeiffer, R, Davies, B, Andorin, A, Hofman, N, Dagradi, F, Pedrazzini, M, Tester, D, Bos, J, Sarquella-Brugada, G, Campuzano, Ó, Platonov, P, Stallmeyer, B, Zumhagen, S, Nannenberg, E, Veldink, J, van den Berg, L, Al-Chalabi, A, Shaw, C, Shaw, P, Morrison, K, Andersen, P, Müller-Nurasyid, M, Cusi, D, Barlassina, C, Galan, P, Lathrop, M, Munter, M, Werge, T, Ribasés, M, Aung, T, Khor, C, Ozaki, M, Lichtner, P, Meitinger, T, van Tintelen, J, Hoedemaekers, Y, Denjoy, I, Leenhardt, A, Napolitano, C, Shimizu, W, Schott, J, Gourraud, J, Makiyama, T, Ohno, S, Itoh, H, Krahn, A, Antzelevitch, C, Roden, D, Saenen, J, Borggrefe, M, Odening, K, Ellinor, P, Tfelt-Hansen, J, Skinner, J, van den Berg, M, Olesen, M, Brugada, J, Brugada, R, Makita, N, Breckpot, J, Yoshinaga, M, Behr, E, Rydberg, A, Aiba, T, Kääb, S, Priori, S, Guicheney, P, Tan, H, Newton-Cheh, C, Ackerman, M, Schwartz, P, Schulze-Bahr, E, Probst, V, Horie, M, Wilde, A, Tanck, M, Bezzina, C, Lahrouchi N, Tadros R, Crotti L, Mizusawa Y, Postema PG, Beekman L, Walsh R, Hasegawa K, Barc J, Ernsting M, Turkowski KL, Mazzanti A, Beckmann BM, Shimamoto K, Diamant UB, Wijeyeratne YD, Kucho Y, Robyns T, Ishikawa T, Arbelo E, Christiansen M, Winbo A, Jabbari R, Lubitz SA, Steinfurt J, Rudic B, Loeys B, Shoemaker MB, Weeke PE, Pfeiffer R, Davies B, Andorin A, Hofman N, Dagradi F, Pedrazzini M, Tester DJ, Bos JM, Sarquella-Brugada G, Campuzano Ó, Platonov PG, Stallmeyer B, Zumhagen S, Nannenberg EA, Veldink JH, van den Berg LH, Al-Chalabi A, Shaw CE, Shaw PJ, Morrison KE, Andersen PM, Müller-Nurasyid M, Cusi D, Barlassina C, Galan P, Lathrop M, Munter M, Werge T, Ribasés M, Aung T, Khor CC, Ozaki M, Lichtner P, Meitinger T, van Tintelen JP, Hoedemaekers Y, Denjoy I, Leenhardt A, Napolitano C, Shimizu W, Schott JJ, Gourraud JB, Makiyama T, Ohno S, Itoh H, Krahn AD, Antzelevitch C, Roden DM, Saenen J, Borggrefe M, Odening KE, Ellinor PT, Tfelt-Hansen J, Skinner JR, van den Berg MP, Olesen MS, Brugada J, Brugada R, Makita N, Breckpot J, Yoshinaga M, Behr ER, Rydberg A, Aiba T, Kääb S, Priori SG, Guicheney P, Tan HL, Newton-Cheh C, Ackerman MJ, Schwartz PJ, Schulze-Bahr E, Probst V, Horie M, Wilde AA, Tanck MWT, and Bezzina CR.

Abstract

Background: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. Methods: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. Results: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (P5×10-8) near NOS1AP, KCNQ1, and KLF12, and 1 missense variant in KCNE1(p.Asp85Asn) at the suggestive threshold (P10-6). Heritability analyses showed that ≈15% of variance in overall LQTS susceptibility was attributable to common genetic variation (h2SNP 0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (rg=0.40; P=3.2×10-3). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS c

Published
2020

4. SCN5A mutation type and a genetic risk score associate variably with brugada syndrome phenotype in SCN5A families

Author

Wijeyeratne, Y, Tanck, M, Mizusawa, Y, Batchvarov, V, Barc, J, Crotti, L, Bos, J, Tester, D, Muir, A, Veltmann, C, Ohno, S, Page, S, Galvin, J, Tadros, R, Muggenthaler, M, Raju, H, Denjoy, I, Schott, J, Gourraud, J, Skoric-Milosavljevic, D, Nannenberg, E, Redon, R, Papadakis, M, Kyndt, F, Dagradi, F, Castelletti, S, Torchio, M, Meitinger, T, Lichtner, P, Ishikawa, T, Wilde, A, Takahashi, K, Sharma, S, Roden, D, Borggrefe, M, Mckeown, P, Shimizu, W, Horie, M, Makita, N, Aiba, T, Ackerman, M, Schwartz, P, Probst, V, Bezzina, C, Behr, E, Wijeyeratne Y. D., Tanck M. W., Mizusawa Y., Batchvarov V., Barc J., Crotti L., Bos J. M., Tester D. J., Muir A., Veltmann C., Ohno S., Page S. P., Galvin J., Tadros R., Muggenthaler M., Raju H., Denjoy I., Schott J. -J., Gourraud J. -B., Skoric-Milosavljevic D., Nannenberg E. A., Redon R., Papadakis M., Kyndt F., Dagradi F., Castelletti S., Torchio M., Meitinger T., Lichtner P., Ishikawa T., Wilde A. A. M., Takahashi K., Sharma S., Roden D. M., Borggrefe M. M., McKeown P. P., Shimizu W., Horie M., Makita N., Aiba T., Ackerman M. J., Schwartz P. J., Probst V., Bezzina C. R., Behr E. R., Wijeyeratne, Y, Tanck, M, Mizusawa, Y, Batchvarov, V, Barc, J, Crotti, L, Bos, J, Tester, D, Muir, A, Veltmann, C, Ohno, S, Page, S, Galvin, J, Tadros, R, Muggenthaler, M, Raju, H, Denjoy, I, Schott, J, Gourraud, J, Skoric-Milosavljevic, D, Nannenberg, E, Redon, R, Papadakis, M, Kyndt, F, Dagradi, F, Castelletti, S, Torchio, M, Meitinger, T, Lichtner, P, Ishikawa, T, Wilde, A, Takahashi, K, Sharma, S, Roden, D, Borggrefe, M, Mckeown, P, Shimizu, W, Horie, M, Makita, N, Aiba, T, Ackerman, M, Schwartz, P, Probst, V, Bezzina, C, Behr, E, Wijeyeratne Y. D., Tanck M. W., Mizusawa Y., Batchvarov V., Barc J., Crotti L., Bos J. M., Tester D. J., Muir A., Veltmann C., Ohno S., Page S. P., Galvin J., Tadros R., Muggenthaler M., Raju H., Denjoy I., Schott J. -J., Gourraud J. -B., Skoric-Milosavljevic D., Nannenberg E. A., Redon R., Papadakis M., Kyndt F., Dagradi F., Castelletti S., Torchio M., Meitinger T., Lichtner P., Ishikawa T., Wilde A. A. M., Takahashi K., Sharma S., Roden D. M., Borggrefe M. M., McKeown P. P., Shimizu W., Horie M., Makita N., Aiba T., Ackerman M. J., Schwartz P. J., Probst V., Bezzina C. R., and Behr E. R.

Abstract

Background: Brugada syndrome (BrS) is characterized by the type 1 Brugada ECG pattern. Pathogenic rare variants in SCN5A (mutations) are identified in 20% of BrS families in whom incomplete penetrance and genotype-negative phenotype-positive individuals are observed. E1784K-SCN5A is the most common SCN5A mutation identified. We determined the association of a BrS genetic risk score (BrS-GRS) and SCN5A mutation type on BrS phenotype in BrS families with SCN5A mutations. Methods: Subjects with a spontaneous type 1 pattern or positive/negative drug challenge from cohorts harboring SCN5A mutations were recruited from 16 centers (n=312). Single nucleotide polymorphisms previously associated with BrS at genome-wide significance were studied in both cohorts: rs11708996, rs10428132, and rs9388451. An additive linear genetic model for the BrS-GRS was assumed (6 single nucleotide polymorphism risk alleles). Results: In the total population (n=312), BrS-GRS ≥4 risk alleles yielded an odds ratio of 4.15 for BrS phenotype ([95% CI, 1.45-11.85]; P=0.0078). Among SCN5A-positive individuals (n=258), BrS-GRS ≥4 risk alleles yielded an odds ratio of 2.35 ([95% CI, 0.89-6.22]; P=0.0846). In SCN5A-negative relatives (n=54), BrS-GRS ≥4 alleles yielded an odds ratio of 22.29 ([95% CI, 1.84-269.30]; P=0.0146). Among E1784K-SCN5A positive family members (n=79), hosting ≥4 risk alleles gave an odds ratio=5.12 ([95% CI, 1.93-13.62]; P=0.0011). Conclusions: Common genetic variation is associated with variable expressivity of BrS phenotype in SCN5A families, explaining in part incomplete penetrance and genotype-negative phenotype-positive individuals. SCN5A mutation genotype and a BrS-GRS associate with BrS phenotype, but the strength of association varies according to presence of a SCN5A mutation and severity of loss of function.

Published
2020

5. Author Correction: Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility (Nature Genetics, (2022), 54, 3, (232-239), 10.1038/s41588-021-01007-6)

Author

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

Abstract

In the version of this article initially published, Federico Manevy’s name appeared with a middle initial in error. The name has been corrected in the HTML and PDF versions of the article.

Published
2022

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

Author

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

Abstract

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel NaV1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on NaV1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings.

Published
2022

8. Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome .

Author

Lahrouchi, N., Tadros, R., Crotti, L., Mizusawa, Y., Postema, P.G., Beekman, L., Walsh, R., Hasegawa, K., Barc, J., Ernsting, M., Turkowski, K.L., Mazzanti, A., Beckmann, B.M., Shimamoto, K., Diamant, U.B., Wijeyeratne, Y.D., Kucho, Y., Robyns, T., Ishikawa, T., Arbelo, E., Christiansen, M., Winbo, A., Jabbari, R., Lubitz, S.A., Steinfurt, J., Rudic, B., Loeys, B., Shoemaker, M.B., Weeke, P.E., Pfeiffer, R., Davies, B., Andorin, A., Hofman, N., Dagradi, F., Pedrazzini, M., Tester, D.J., Bos, J.M, Sarquella-Brugada, G., Campuzano, Ó., Platonov, P.G., Stallmeyer, B., Zumhagen, S., Nannenberg, E.A., Veldink, J.H., Berg, L.H. van den, Al-Chalabi, A., Shaw, C.E., Shaw, P.J., Morrison, K.E., Andersen, P.M., Müller-Nurasyid, M., Cusi, D., Barlassina, C., Galan, P., Lathrop, M., Munter, M., Werge, T., Ribasés, M., Aung, T., Khor, C.C., Ozaki, M., Lichtner, P., Meitinger, T., Tintelen, J.P. van, Hoedemaekers, Y.M., Denjoy, I., Leenhardt, A., Napolitano, C., Shimizu, W., Schott, J.J., Gourraud, J.B., Makiyama, T., Ohno, S., Itoh, H., Krahn, A.D., Antzelevitch, C., Roden, D.M., Saenen, J., Borggrefe, M., Odening, K.E., Ellinor, P.T., Tfelt-Hansen, J., Skinner, J.R., Berg, M.P., Olesen, M.S., Brugada, J., Brugada, R., Makita, N., Breckpot, J., Yoshinaga, M., Behr, E.R., Rydberg, A., Aiba, T., Kääb, S., Priori, S.G., Guicheney, P., Tan, H.L., Newton-Cheh, C., Ackerman, M.J., Schwartz, P.J., Lahrouchi, N., Tadros, R., Crotti, L., Mizusawa, Y., Postema, P.G., Beekman, L., Walsh, R., Hasegawa, K., Barc, J., Ernsting, M., Turkowski, K.L., Mazzanti, A., Beckmann, B.M., Shimamoto, K., Diamant, U.B., Wijeyeratne, Y.D., Kucho, Y., Robyns, T., Ishikawa, T., Arbelo, E., Christiansen, M., Winbo, A., Jabbari, R., Lubitz, S.A., Steinfurt, J., Rudic, B., Loeys, B., Shoemaker, M.B., Weeke, P.E., Pfeiffer, R., Davies, B., Andorin, A., Hofman, N., Dagradi, F., Pedrazzini, M., Tester, D.J., Bos, J.M, Sarquella-Brugada, G., Campuzano, Ó., Platonov, P.G., Stallmeyer, B., Zumhagen, S., Nannenberg, E.A., Veldink, J.H., Berg, L.H. van den, Al-Chalabi, A., Shaw, C.E., Shaw, P.J., Morrison, K.E., Andersen, P.M., Müller-Nurasyid, M., Cusi, D., Barlassina, C., Galan, P., Lathrop, M., Munter, M., Werge, T., Ribasés, M., Aung, T., Khor, C.C., Ozaki, M., Lichtner, P., Meitinger, T., Tintelen, J.P. van, Hoedemaekers, Y.M., Denjoy, I., Leenhardt, A., Napolitano, C., Shimizu, W., Schott, J.J., Gourraud, J.B., Makiyama, T., Ohno, S., Itoh, H., Krahn, A.D., Antzelevitch, C., Roden, D.M., Saenen, J., Borggrefe, M., Odening, K.E., Ellinor, P.T., Tfelt-Hansen, J., Skinner, J.R., Berg, M.P., Olesen, M.S., Brugada, J., Brugada, R., Makita, N., Breckpot, J., Yoshinaga, M., Behr, E.R., Rydberg, A., Aiba, T., Kääb, S., Priori, S.G., Guicheney, P., Tan, H.L., Newton-Cheh, C., Ackerman, M.J., and Schwartz, P.J.

Abstract

Contains fulltext : 230155.pdf (Publisher’s version ) (Open Access)

Published
2020

11. Randomized trial of angiotensin II-receptor blocker vs. dihydropiridine calcium channel blocker in the treatment of paroxysmal atrial fibrillation with hypertension (J-RHYTHM II Study)

Author

Yamashita, Takeshi, Inoue, Hiroshi, Okumura, Ken, Kodama, Itsuo, Aizawa, Yoshifusa, Atarashi, Hirotsugu, Ohe, Tohru, Ohtsu, Hiroshi, Kato, Takao, Kamakura, Shiro, Kumagai, Koichiro, Kurachi, Yoshihisa, Koretsune, Yukihiro, Saikawa, Tetsunori, Sakurai, Masayuki, Sato, Toshiaki, Sugi, Kaoru, Nakaya, Haruaki, Hirai, Makoto, Hirayama, Atsushi, Fukatani, Masahiko, Mitamura, Hideo, Yamazaki, Tsutomu, Watanabe, Eiichi, Ogawa, Satoshi, Katoh, T, Igawa, O, Matsumoto, N, Yamashita, T, Kaneko, Y, Watanabe, E, Ogawa, S, Osaka, T, Fujii, E, Niwano, S, Yoshioka, K, Kato, M, Okazaki, O, Kusano, K, Okuyama, Y, Furushima, H, Suzuki, M, Noda, T, Kawara, T, Sato, T, Kamakura, S, Endoh, Y, Kumagai, K, Hiyoshi, Y, Ishiyama, T, Ohtsuka, T, Matsumoto, M, Chishaki, A, Shinohara, T, Shirayama, T, Koretsune, Y, Yokoyama, E, Ajiki, K, Fujio, K, Sugi, K, Yamakawa, T, Yusu, S, Inoue, H, Kawamura, Y, Hayano, M, Date, T, Mizusawa, Y, Kobayashi, Y, Satomi, K, Imai, Y, Atarashi, H, Fukunami, M, Yokoshiki, H, Betsuyaku, T, Okumura, K, Takeda, H, Matsumoto, K, Okishige, K, Tagawa, M, Hirai, M, and Okazaki, H

Published
2011
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14. Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death

Author

Bezzina, C, Barc, J, Mizusawa, Y, Remme, C, Gourraud, J, Simonet, F, Verkerk, A, Schwartz, P, Crotti, L, Dagradi, F, Guicheney, P, Fressart, V, Leenhardt, A, Antzelevitch, C, Bartkowiak, S, Borggrefe, M, Schimpf, R, Schulze-Bahr, E, Zumhagen, S, Behr, E, Bastiaenen, R, Tfelt-Hansen, J, Olesen, M, Kääb, S, Beckmann, B, Weeke, P, Watanabe, H, Endo, N, Minamino, T, Horie, M, Ohno, S, Hasegawa, K, Makita, N, Nogami, A, Shimizu, W, Aiba, T, Froguel, P, Balkau, B, Lantieri, O, Torchio, M, Wiese, C, Weber, D, Wolswinkel, R, Coronel, R, Boukens, B, Bézieau, S, Charpentier, E, Chatel, S, Despres, A, Gros, F, Kyndt, F, Lecointe, S, Lindenbaum, P, Portero, V, Violleau, J, Gessler, M, Tan, H, Roden, D, Christoffels, V, Le Marec, H, Wilde, A, Probst, V, Schott, J, Dina, C, Redon, R, Bezzina CR., Barc J., Mizusawa Y., Remme CA., Gourraud JB., Simonet F., Verkerk AO., Schwartz PJ., Crotti L., Dagradi F., Guicheney P., Fressart V., Leenhardt A., Antzelevitch C., Bartkowiak S., Borggrefe M., Schimpf R., Schulze-Bahr E., Zumhagen S., Behr ER., Bastiaenen R., Tfelt-Hansen J., Olesen MS., Kääb S., Beckmann BM., Weeke P., Watanabe H., Endo N., Minamino T., Horie M., Ohno S., Hasegawa K., Makita N., Nogami A., Shimizu W., Aiba T., Froguel P., Balkau B., Lantieri O., Torchio M., Wiese C., Weber D., Wolswinkel R., Coronel R., Boukens BJ., Bézieau S., Charpentier E., Chatel S., Despres A., Gros F., Kyndt F., Lecointe S., Lindenbaum P., Portero V., Violleau J., Gessler M., Tan HL., Roden DM., Christoffels VM., Le Marec H., Wilde AA., Probst V., Schott JJ., Dina C., Redon R., Bezzina, C, Barc, J, Mizusawa, Y, Remme, C, Gourraud, J, Simonet, F, Verkerk, A, Schwartz, P, Crotti, L, Dagradi, F, Guicheney, P, Fressart, V, Leenhardt, A, Antzelevitch, C, Bartkowiak, S, Borggrefe, M, Schimpf, R, Schulze-Bahr, E, Zumhagen, S, Behr, E, Bastiaenen, R, Tfelt-Hansen, J, Olesen, M, Kääb, S, Beckmann, B, Weeke, P, Watanabe, H, Endo, N, Minamino, T, Horie, M, Ohno, S, Hasegawa, K, Makita, N, Nogami, A, Shimizu, W, Aiba, T, Froguel, P, Balkau, B, Lantieri, O, Torchio, M, Wiese, C, Weber, D, Wolswinkel, R, Coronel, R, Boukens, B, Bézieau, S, Charpentier, E, Chatel, S, Despres, A, Gros, F, Kyndt, F, Lecointe, S, Lindenbaum, P, Portero, V, Violleau, J, Gessler, M, Tan, H, Roden, D, Christoffels, V, Le Marec, H, Wilde, A, Probst, V, Schott, J, Dina, C, Redon, R, Bezzina CR., Barc J., Mizusawa Y., Remme CA., Gourraud JB., Simonet F., Verkerk AO., Schwartz PJ., Crotti L., Dagradi F., Guicheney P., Fressart V., Leenhardt A., Antzelevitch C., Bartkowiak S., Borggrefe M., Schimpf R., Schulze-Bahr E., Zumhagen S., Behr ER., Bastiaenen R., Tfelt-Hansen J., Olesen MS., Kääb S., Beckmann BM., Weeke P., Watanabe H., Endo N., Minamino T., Horie M., Ohno S., Hasegawa K., Makita N., Nogami A., Shimizu W., Aiba T., Froguel P., Balkau B., Lantieri O., Torchio M., Wiese C., Weber D., Wolswinkel R., Coronel R., Boukens BJ., Bézieau S., Charpentier E., Chatel S., Despres A., Gros F., Kyndt F., Lecointe S., Lindenbaum P., Portero V., Violleau J., Gessler M., Tan HL., Roden DM., Christoffels VM., Le Marec H., Wilde AA., Probst V., Schott JJ., Dina C., and Redon R.

Abstract

Brugada syndrome is a rare cardiac arrhythmia disorder, causally related to SCN5A mutations in around 20% of cases. Through a genome-wide association study of 312 individuals with Brugada syndrome and 1,115 controls, we detected 2 significant association signals at the SCN10A locus (rs10428132) and near the HEY2 gene (rs9388451). Independent replication confirmed both signals (meta-analyses: rs10428132, P = 1.0 × 10 -68; rs9388451, P = 5.1 × 10 -17) and identified one additional signal in SCN5A (at 3p21; rs11708996, P = 1.0 × 10 -14). The cumulative effect of the three loci on disease susceptibility was unexpectedly large (P trend = 6.1 × 10 -81). The association signals at SCN5A-SCN10A demonstrate that genetic polymorphisms modulating cardiac conduction can also influence susceptibility to cardiac arrhythmia. The implication of association with HEY2, supported by new evidence that Hey2 regulates cardiac electrical activity, shows that Brugada syndrome may originate from altered transcriptional programming during cardiac development. Altogether, our findings indicate that common genetic variation can have a strong impact on the predisposition to rare diseases

Published
2013

15. Role of common and rare variants in SCN10A: results from the Brugada syndrome QRS locus gene discovery collaborative study

Author

Behr, E, Savio-Galimberti, E, Barc, J, Holst, A, Petropoulou, E, Prins, B, Jabbari, J, Torchio, M, Berthet, M, Mizusawa, Y, Yang, T, Nannenberg, E, Dagradi, F, Weeke, P, Bastiaenan, R, Ackerman, M, Haunso, S, Leenhardt, A, Kääb, S, Probst, V, Redon, R, Sharma, S, Wilde, A, Tfelt-Hansen, J, Schwartz, P, Roden, D, Bezzina, C, Olesen, M, Darbar, D, Guicheney, P, Crotti, L, Jamshidi, Y, Holst, AG, Behr, E, Savio-Galimberti, E, Barc, J, Holst, A, Petropoulou, E, Prins, B, Jabbari, J, Torchio, M, Berthet, M, Mizusawa, Y, Yang, T, Nannenberg, E, Dagradi, F, Weeke, P, Bastiaenan, R, Ackerman, M, Haunso, S, Leenhardt, A, Kääb, S, Probst, V, Redon, R, Sharma, S, Wilde, A, Tfelt-Hansen, J, Schwartz, P, Roden, D, Bezzina, C, Olesen, M, Darbar, D, Guicheney, P, Crotti, L, Jamshidi, Y, and Holst, AG

Abstract

Aims: Brugada syndrome (BrS) remains genetically heterogeneous and is associated with slowed cardiac conduction. We aimed to identify genetic variation in BrS cases at loci associated with QRS duration. Methods and results: A multi-centre study sequenced seven candidate genes (SCN10A, HAND1, PLN, CASQ2, TKT, TBX3, and TBX5) in 156 Caucasian SCN5A mutation-negative BrS patients (80% male; mean age 48) with symptoms (64%) and/or a family history of sudden death (47%) or BrS (18%). Forty-nine variants were identified: 18 were rare (MAF <1%) and non-synonymous; and 11/18 (61.1%), mostly in SCN10A, were predicted as pathogenic using multiple bioinformatics tools. Allele frequencies were compared with the Exome Sequencing and UK10K Projects. SKAT methods tested rare variation in SCN10A finding no statistically significant difference between cases and controls. Co-segregation analysis was possible for four of seven probands carrying a novel pathogenic variant. Only one pedigree (I671V/G1299A in SCN10A) showed co-segregation. The SCN10A SNP V1073 was, however, associated strongly with BrS [66.9 vs. 40.1% (UK10K) OR (95% CI) = 3.02 (2.35-3.87), P = 8.07 × 10-19]. Voltage-clamp experiments for NaV1.8 were performed for SCN10A common variants V1073, A1073, and rare variants of interest: A200V and I671V. V1073, A200V and I671V, demonstrated significant reductions in peak INa compared with ancestral allele A1073 (rs6795970). Conclusion: Rare variants in the screened QRS-associated genes (including SCN10A) are not responsible for a significant proportion of SCN5A mutation negative BrS. The common SNP SCN10A V1073 was strongly associated with BrS and demonstrated loss of NaV1.8 function, as did rare variants in isolated patients.

Published
2015

16. The effect of blue-blocking intraocular lenses on circadian biological rhythm: protocol for a randomised controlled trial (CLOCK-IOL colour study)

Author

Nishi, T., primary, Saeki, K., additional, Obayashi, K., additional, Miyata, K., additional, Tone, N., additional, Tsujinaka, H., additional, Yamashita, M., additional, Masuda, N., additional, Mizusawa, Y., additional, Okamoto, M., additional, Hasegawa, T., additional, Maruoka, S., additional, Ueda, T., additional, Kojima, M., additional, Matsuura, T., additional, Kurumatani, N., additional, and Ogata, N., additional

Published
2015
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17. Characterization of SEMA3A-encoded semaphorin as a naturally cccurring Kv4.3 protein inhibitor and its contribution to Brugada Syndrome

Author

Boczek, N, Ye, D, Johnson, E, Wang, W, Crotti, L, Tester, D, Dagradi, F, Mizusawa, Y, Torchio, M, Alders, M, Giudicessi, J, Wilde, A, Schwartz, P, Nerbonne, J, Ackerman, M, Boczek, NJ, Johnson, EK, Tester, DJ, Giudicessi, JR, Wilde, AA, Schwartz, PJ, Nerbonne, JM, Ackerman, MJ, Boczek, N, Ye, D, Johnson, E, Wang, W, Crotti, L, Tester, D, Dagradi, F, Mizusawa, Y, Torchio, M, Alders, M, Giudicessi, J, Wilde, A, Schwartz, P, Nerbonne, J, Ackerman, M, Boczek, NJ, Johnson, EK, Tester, DJ, Giudicessi, JR, Wilde, AA, Schwartz, PJ, Nerbonne, JM, and Ackerman, MJ

Abstract

Rationale: Semaphorin 3A (SEMA3A)-encoded semaphorin is a chemorepellent that disrupts neural patterning in the nervous and cardiac systems. In addition, SEMA3A has an amino acid motif that is analogous to hanatoxin, an inhibitor of voltage-gated K+ channels. SEMA3A-knockout mice exhibit an abnormal ECG pattern and are prone to ventricular arrhythmias and sudden cardiac death. Objective: Our aim was to determine whether SEMA3A is a naturally occurring protein inhibitor of K(v)4.3 (I-to) channels and its potential contribution to Brugada syndrome. Methods and Results: K(v)4.3, Na(v)1.5, Ca(v)1.2, or K(v)4.2 were coexpressed or perfused with SEMA3A in HEK293 cells, and electrophysiological properties were examined via whole-cell patch clamp technique. SEMA3A selectively altered K(v)4.3 by significantly reducing peak current density without perturbing K(v)4.3 cell surface protein expression. SEMA3A also reduced I-to current density in cardiomyocytes derived from human-induced pluripotent stem cells. Disruption of a putative toxin binding domain on K(v)4.3 was used to assess physical interactions between SEMA3A and K(v)4.3. These findings in combination with coimmunoprecipitations of SEMA3A and K(v)4.3 revealed a potential direct binding interaction between these proteins. Comprehensive mutational analysis of SEMA3A was performed on 198 unrelated SCN5A genotype-negative patients with Brugada syndrome, and 2 rare SEMA3A missense mutations were identified. The SEMA3A mutations disrupted SEMA3A's ability to inhibit K(v)4.3 channels, resulting in a significant gain of K(v)4.3 current compared with wild-type SEMA3A. Conclusions: This study is the first to demonstrate SEMA3A as a naturally occurring protein that selectively inhibits K(v)4.3 and SEMA3A as a possible Brugada syndrome susceptibility gene through a K(v)4.3 gain-of-function mechanism

Published
2014

18. Rationale and design of the PRAETORIAN trial: a Prospective, RAndomizEd comparison of subcuTaneOus and tRansvenous ImplANtable cardioverter-defibrillator therapy.

Author

Olde Nordkamp, M.A.M., Knops, R.E., Bardy, G.H., Blaauw, Y., Boersma, L.V., Bos, J.S., Delnoy, P.P.H.M., Dessel, P.F. van, Driessen, A.H., Groot, J.R. de, Herrman, J.P., Jordaens, L.J., Kooiman, K.M., Maass, A.H., Meine, M., Mizusawa, Y., Molhoek, S.G., Opstal, A.J. van, Tijssen, J.G.P., Wilde, A.A., Olde Nordkamp, M.A.M., Knops, R.E., Bardy, G.H., Blaauw, Y., Boersma, L.V., Bos, J.S., Delnoy, P.P.H.M., Dessel, P.F. van, Driessen, A.H., Groot, J.R. de, Herrman, J.P., Jordaens, L.J., Kooiman, K.M., Maass, A.H., Meine, M., Mizusawa, Y., Molhoek, S.G., Opstal, A.J. van, Tijssen, J.G.P., and Wilde, A.A.

Abstract

01 mei 2012, Item does not contain fulltext

Published
2012

19. Rationale and design of the PRAETORIAN trial: A Prospective, RAndomizEd comparison of subcuTaneOus and tRansvenous ImplANtable cardioverter- defibrillator therapy

Author

Olde Nordkamp, L.R.A. (Louise R.A.), Knops, R.E. (Reinoud), Bardy, G.H. (Gust), Blaauw, Y. (Yuri), Boersma, L. (Lucas), Bos, J.S. (Johannes), Delnoy, P.P.H.M. (Peter Paul), Pascal, P.F.H.M. van, Driessen, A.H.G. (Antoine), Groot, J.R. (Joris) de, Herrman, J.P.R., Jordaens, L.J.L.M. (Luc), Kooiman, K.M. (Kirsten), Maass, A.H. (Alexander), Meine, M. (Mathias), Mizusawa, Y. (Yuka), Molhoek, S.G. (Sander), Opstal, J. (Jurjen) van, Tijssen, J.G.P. (Jan), Wilde, A.A.M. (Arthur), Olde Nordkamp, L.R.A. (Louise R.A.), Knops, R.E. (Reinoud), Bardy, G.H. (Gust), Blaauw, Y. (Yuri), Boersma, L. (Lucas), Bos, J.S. (Johannes), Delnoy, P.P.H.M. (Peter Paul), Pascal, P.F.H.M. van, Driessen, A.H.G. (Antoine), Groot, J.R. (Joris) de, Herrman, J.P.R., Jordaens, L.J.L.M. (Luc), Kooiman, K.M. (Kirsten), Maass, A.H. (Alexander), Meine, M. (Mathias), Mizusawa, Y. (Yuka), Molhoek, S.G. (Sander), Opstal, J. (Jurjen) van, Tijssen, J.G.P. (Jan), and Wilde, A.A.M. (Arthur)

Abstract

Background: Implantable cardioverter-defibrillators (ICDs) are widely used to prevent fatal outcomes associated with life-threatening arrhythmic episodes in a variety of cardiac diseases. These ICDs rely on transvenous leads for cardiac sensing and defibrillation. A new entirely subcutaneous ICD overcomes problems associated with transvenous leads. However, the role of the subcutaneous ICD as an adjunctive or primary therapy in patients at risk for sudden cardiac death is unclear. Study Design: The PRAETORIAN trial is an investigator-initiated, randomized, controlled, multicenter, prospective 2-arm trial that outlines the advantages and disadvantages of the subcutaneous ICD. Patients with a class I or IIa indication for ICD therapy without an indication for bradypacing or tachypacing are included. A total of 700 patients are randomized to either the subcutaneous or transvenous ICD (1:1). The study is powered to claim noninferiority of the subcutaneous ICD with respect to the composite primary endpoint of inappropriate shocks and ICD-related complications. After noninferiority is established, statistical analysis is done for potential superiority. Secondary endpoint comparisons of shock efficacy and patient mortality are also made. Conclusion: The PRAETORIAN trial is a randomized trial that aims to gain scientific evidence for the use of the subcutaneous ICD compared with the transvenous ICD in a population of patients with conventional ICD with respect to major ICD-related adverse events. This trial is registered at ClinicalTrials.gov with trial ID NCT01296022.

Published
2012
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20. Genome-Wide Association Analysis Identifies 3 Common Variants Predisposing to Brugada Syndrome, a Rare Disease with High Risk of Sudden Cardiac Death

Author

Barc, J., primary, Bezzina, C., additional, Mizusawa, Y., additional, Remme, C., additional, Gourraud, J., additional, Verkerk, A., additional, Schwartz, P., additional, Guicheney, P., additional, Antzelevitch, C., additional, Schulze-Bahr, E., additional, Behr, E., additional, Tfelt-Hanson, J., additional, Kaab, S., additional, Watanabe, H., additional, Horie, M., additional, Makita, N., additional, Shimizu, W., additional, Roden, D., additional, Christoffels, V., additional, Gessler, M., additional, Wilde, A., additional, Probst, V., additional, Schott, J., additional, Dina, C., additional, and Redon, R., additional

Published
2013
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23. Session 61: Effects of interventions on embryo quality

Author

Naik, R., primary, Bahadur, G., additional, Olivier, F., additional, Srikantharajah, A., additional, Mehta, J., additional, Joshi, H., additional, Shapiro, B., additional, Daneshmand, S., additional, Garner, F., additional, Aguirre, M., additional, Hudson, C., additional, Catt, S., additional, Lingham, E., additional, Lee, W., additional, Muthusamy, Y., additional, Kally, C., additional, Chen, P., additional, Pangestu, M., additional, Catt, J., additional, Temple-Smith, P., additional, Kailasam, C., additional, Gordon, U. D., additional, Kobayashi, M., additional, Yoshida, A., additional, Tanigiwa, S., additional, Seida, K., additional, Suzuki, H., additional, Tanaka, M., additional, Ogata, S., additional, Matsu-ura, M., additional, Ogata, H., additional, Kajiwara, A., additional, Tokura, Y., additional, Matsumoto, Y., additional, Mizusawa, Y., additional, Okamoto, E., additional, Yamada, S., additional, Kokeguchi, S., additional, Shiotani, M., additional, Grassa, L. H., additional, Marin, S. P., additional, Barragan, S. A., additional, Lorite, J. A., additional, Campos, F. B., additional, and Garcia-Velasco, J. A., additional

Published
2013
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25. QUALITY AND SAFETY OF ART THERAPIES

Author

Caballero, P., primary, Alonso, J., additional, Cortes, S., additional, Caballero Campo, M., additional, Gago, M., additional, Nunez-Calonge, R., additional, Ricciarelli, E., additional, Gomez Palomares, J. L., additional, Bruna Catalan, I., additional, Hernandez, E. R., additional, Grzegorczyk-Martin, V., additional, Belaisch-Allart, J., additional, Mayenga, J. M., additional, Kulski, O., additional, Plachot, M., additional, Darby, H. C., additional, Florensa Bargallo, M., additional, Perals Vazquez, N., additional, Esbert Algam, M., additional, Belles Fernandez, M., additional, Ballesteros Boluda, A., additional, Calderon de Oya, G., additional, Alegre de Miquel, M., additional, Choudhary, M., additional, Ramineni, A., additional, Stewart, J., additional, Cabello, Y., additional, Fernandez-Shaw, S., additional, Mercader, A., additional, Herrer, R., additional, Arroyo, G., additional, Del Rio, F., additional, Carrera, M., additional, Fernandez Sanchez, M., additional, Sumimoto, T., additional, Kataoka, N., additional, Ogata, H., additional, Mizuta, S., additional, Tokura, Y., additional, Yamada, S., additional, Ogata, S., additional, Mizusawa, Y., additional, Matsumoto, Y., additional, Okamoto, E., additional, Kokeguchi, S., additional, Shiotani, M., additional, Nagai, Y., additional, Otsuki, J., additional, Maeda, K., additional, Momma, Y., additional, Takahashi, K., additional, Chuko, M., additional, Miwa, A., additional, Nagai, A., additional, Seggers, J., additional, Haadsma, M. L., additional, La Bastide-van Gemert, S., additional, Heineman, M. J., additional, Kok, J. H., additional, Middelburg, K. J., additional, Roseboom, T. J., additional, Schendelaar, P., additional, Van den Heuvel, E. R., additional, Hadders-Algra, M., additional, Jongbloed-Pereboom, M., additional, La Bastide-Van Gemert, S., additional, Heineman, K. R., additional, Bos, A. F., additional, Kondapalli, L. A., additional, Shaunik, A., additional, Molinaro, T. A., additional, Ratcliffe, S. J., additional, Barnhart, K. T., additional, Haadsma, M., additional, Keating, P., additional, Van Hoften, J. C., additional, Veenstra-Knol, H. E., additional, Cobben, J. M., additional, Pirkevi, C., additional, Atayurt, Z., additional, Yelke, H., additional, Kahraman, S., additional, Desmyttere, S., additional, Verpoest, W., additional, Haentjens, P., additional, Verheyen, G., additional, Liebaers, I., additional, Bonduelle, M., additional, Winter, C., additional, Van Acker, F., additional, De Schrijver, F., additional, Nekkebroeck, J., additional, Pariente-Khayat, A., additional, de Laubier, A., additional, Fehily, D., additional, Lemardeley, G., additional, Merlet, F., additional, Creusvaux, H., additional, Nakajo, Y., additional, Sakamoto, E., additional, Doshida, M., additional, Toya, M., additional, Nasu, I., additional, Kyono, K., additional, Schats, R., additional, Vergouw, C. G., additional, Kostelijk, E. H., additional, Doejaaren, E., additional, Hompes, P. G. A., additional, Lambalk, C. B., additional, Nakamura, Y., additional, Takisawa, T., additional, Shibuya, Y., additional, Sato, Y., additional, Sato, K., additional, Berard, A., additional, Chaabane, S., additional, Sheehy, O., additional, Blais, L., additional, Fraser, W., additional, Bissonnette, F., additional, Monnier, P., additional, Tan, S. L., additional, Trasler, J., additional, Subramaniam, A., additional, Chiappetta, R., additional, Mania, A., additional, Trew, G., additional, Lavery, S. A., additional, van den Akker, O., additional, Purewal, S., additional, Bunnell, C., additional, Lashen, H., additional, Terriou, P., additional, Giorgetti, C., additional, Porcu-Buisson, G., additional, Roger, V., additional, Chinchole, J. M., additional, Hamon, V., additional, Allemand-Sourieu, J., additional, Cravello, L., additional, Moreau, J., additional, Chabert-Orsini, V., additional, Belva, F., additional, Roelants, M., additional, De Schepper, J., additional, Devroey, P., additional, Painter, R. C., additional, Machin, L., additional, Fearon, K., additional, Morishima, K., additional, Fujimoto, A., additional, Oishi, H., additional, Hirata, T., additional, Harada, M., additional, Hasegawa, A., additional, Osuga, Y., additional, Yano, T., additional, Kozuma, S., additional, and Taketani, Y., additional

Published
2012
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26. EARLY PREGNANCY

Author

Chakraborty, P., primary, Chakravarty, B. N., additional, Kabir, S. N., additional, Goswami, S. K., additional, Yenicesu, O., additional, Gulerman, C., additional, Ozyer, S., additional, Cakar, E., additional, Sarikaya, E., additional, Mollamahmutoglu, L., additional, Daponte, A., additional, Deligeoroglou, E., additional, Pournaras, S., additional, Tsezou, A., additional, Garas, A., additional, Skentou, H., additional, Messinis, I. E., additional, Ganesh, A., additional, Chowdhuri, K., additional, Shyam, T., additional, Ghosh, S., additional, Chattopadhyay, R., additional, Banerjee, P., additional, Pasricha, P., additional, Chaudhury, K., additional, Kuji, N., additional, Kitamura, S., additional, Mochimaru, Y., additional, Yamada, M., additional, Hamatani, T., additional, Kawakami, M., additional, Hirayama, A., additional, Sugimoto, M., additional, Soga, T., additional, Tomita, M., additional, Yoshimura, Y., additional, Tabibi, A., additional, Tarahhomi, M., additional, Roghayee, M., additional, Bayatsarmadi, H., additional, Zolghadri, J., additional, Younesi, M., additional, Bug, S., additional, Solfrank, B., additional, Pricelius, J., additional, Craig, A., additional, Botcherby, M., additional, Stecher, M., additional, Bingemann, S., additional, Becker, B., additional, Nevinny-Stickel-Hinzpeter, C., additional, Kuroda, K., additional, Venkatakrishnan, R., additional, Salker, M. S., additional, Quenby, S., additional, Brosens, J. J., additional, Rahmati, M., additional, Petitbarat, M., additional, Dubanchet, S., additional, Chaouat, G., additional, Ledee, N., additional, van den Berg, M., additional, van Maarle, M. C., additional, van Wely, M., additional, Goddijn, M., additional, Telli, P., additional, Erdem, M., additional, Bozkurt, N., additional, Oktem, M., additional, Yirmibes K., M., additional, Karabacak, O., additional, Erdem, A., additional, Kim, C. H., additional, Lee, K. H., additional, Kim, S. H., additional, Chae, H. D., additional, Kang, B. M., additional, Jung, K. S., additional, Johnson, S., additional, Godbert, S., additional, Perry, P., additional, Parkinson, P., additional, Vink-Ranti, C. Q. J., additional, Van Os, H. C., additional, Tucker, K. E., additional, Kapiteijn, K., additional, Heijdra, P. M. A., additional, Jansen, C. A. M., additional, Matsumoto, H., additional, Sato, Y., additional, Suginami, K., additional, Horie, A., additional, Fujiwara, H., additional, Konishi, I., additional, Yamada, S., additional, Kataoka, N., additional, Ogata, S., additional, Mukai, M., additional, Inai, K., additional, Hashimoto, H., additional, Tokura, Y., additional, Mizusawa, Y., additional, Matsumoto, Y., additional, Okamoto, E., additional, Kokeguchi, S., additional, Shiotani, M., additional, Mariee, N., additional, Li, T. C., additional, Laird, S. M., additional, Refaat, B., additional, Simpson, H., additional, Ledger, W., additional, Confino, E., additional, Williams, A., additional, Grabar, V., additional, Feskov, A., additional, Feskova, I., additional, Blazhko, E., additional, Maruyama, M., additional, Hattori, A., additional, Chi, H. B., additional, Qiao, J., additional, Wang, H. N., additional, Hong, T. P., additional, Gao, H. W., additional, Abdelnaby El Gelany, S. A. A., additional, Nady Abdelmegeed, A., additional, Markoff, A., additional, Rogenhofer, N., additional, Engels, L., additional, Bogdanova, N., additional, Tuettelmann, F., additional, Thaler, C., additional, Seckin, B., additional, Sargin Oruc, A., additional, Celen, S., additional, Cicek, N., additional, Zarei, S., additional, Torabi, R., additional, Zeraati, H., additional, Zarnani, A. H., additional, Akhondi, M. M., additional, Hadavi, R., additional, Savadi-Shiraz, E., additional, Jeddi-Tehrani, M., additional, Sugiura-Ogasawara, M., additional, Ozaki, Y., additional, Katano, K., additional, Suzumori, N., additional, Kitaori, T., additional, Mizutani, E., additional, Al-Gubory, K. H., additional, Bolifraud, P., additional, Angele, K., additional, Grange, S., additional, Puillet-Anselme, L., additional, and Garrel, C., additional

Published
2012
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28. POSTER VIEWING SESSION - EMBRYOLOGY

Author

Fourati Ben Mustapha, S., primary, Khrouf, M., additional, Kacem Ben Rejeb, K., additional, Elloumi Chaabene, H., additional, Merdassi, G., additional, Wahbi, D., additional, Ben Meftah, M., additional, Zhioua, F., additional, Zhioua, A., additional, Azzarello, A., additional, Host, T., additional, Mikkelsen, A. L., additional, Theofanakis, C. P., additional, Dinopoulou, V., additional, Mavrogianni, D., additional, Partsinevelos, G. A., additional, Drakakis, P., additional, Stefanidis, K., additional, Bletsa, A., additional, Loutradis, D., additional, Rienzi, L., additional, Cobo, A., additional, Paffoni, A., additional, Scarduelli, C., additional, Capalbo, A., additional, Garrido, N., additional, Remohi, J., additional, Ragni, G., additional, Ubaldi, F. M., additional, Herrer, R., additional, Quera, M., additional, GIL, E., additional, Serna, J., additional, Grondahl, M. L., additional, Bogstad, J., additional, Agerholm, I. E., additional, Lemmen, J. G., additional, Bentin-Ley, U., additional, Lundstrom, P., additional, Kesmodel, U. S., additional, Raaschou-Jensen, M., additional, Ladelund, S., additional, Guzman, L., additional, Ortega, C., additional, Albuz, F. K., additional, Gilchrist, R. B., additional, Devroey, P., additional, Smitz, J., additional, De Vos, M., additional, Bielanska, M., additional, Leveille, M. C., additional, Borghi, E., additional, Magli, M. C., additional, Figueroa, M. J., additional, Mascaretti, G., additional, Ferraretti, A. P., additional, Gianaroli, L., additional, Szlit, E., additional, Leocata Nieto, F., additional, Maggiotto, G., additional, Arenas, G., additional, Tarducci Bonfiglio, N., additional, Ahumada, A., additional, Asch, R., additional, Sciorio, R., additional, Dayoub, N., additional, Thong, J., additional, Pickering, S., additional, Ten, J., additional, Carracedo, M. A., additional, Guerrero, J., additional, Rodriguez-Arnedo, A., additional, Llacer, J., additional, Bernabeu, R., additional, Tatone, C., additional, Heizenrieder, T., additional, Di Emidio, G., additional, Treffon, P., additional, Seidel, T., additional, Eichenlaub-Ritter, U., additional, Cortezzi, S. S., additional, Cabral, E. C., additional, Ferreira, C. R., additional, Trevisan, M. G., additional, Figueira, R. C. S., additional, Braga, D. P. A. F., additional, Eberlin, M. N., additional, Iaconelli Jr., A., additional, Borges Jr., E., additional, Zabala, A., additional, Pessino, T., additional, Blanco, L., additional, Rey Valzacchi, G., additional, Leocata, F., additional, Vanden Meerschaut, F., additional, Heindryckx, B., additional, Qian, C., additional, Deforce, D., additional, Leybaert, L., additional, De Sutter, P., additional, De las Heras, M., additional, De Pablo, J. L., additional, Navarro, B., additional, Agirregoikoa, J. A., additional, Barrenetxea, G., additional, Cruz, M., additional, Perez-Cano, I., additional, Gadea, B., additional, Herrero, J., additional, Martinez, M., additional, Roldan, M., additional, Munoz, M., additional, Pellicer, A., additional, Meseguer, M., additional, Galindo, N., additional, Scarselli, F., additional, Alviggi, E., additional, Colasante, A., additional, Minasi, M. G., additional, Rubino, P., additional, Lobascio, M., additional, Ferrero, S., additional, Litwicka, K., additional, Varricchio, M. T., additional, Giannini, P., additional, Piscitelli, P., additional, Franco, G., additional, Zavaglia, D., additional, Nagy, Z. P., additional, Greco, E., additional, Urner, F., additional, Wirthner, D., additional, Murisier, F., additional, Mock, P., additional, Germond, M., additional, Amorocho Llanos, B., additional, Calderon, G., additional, Lopez, D., additional, Fernandez, L., additional, Nicolas, M., additional, Landeras, J., additional, Finn-Sell, S. L., additional, Leandri, R., additional, Fleming, T. P., additional, Macklon, N. S., additional, Cheong, Y. C., additional, Eckert, J. J., additional, Lee, J. H., additional, Jung, Y. J., additional, Hwang, H. K., additional, Kang, A., additional, An, S. J., additional, Jung, J. Y., additional, Kwon, H. C., additional, Lee, S. J., additional, Palini, S., additional, Zolla, L., additional, De Stefani, S., additional, Scala, V., additional, D'Alessandro, A., additional, Polli, V., additional, Rocchi, P., additional, Tiezzi, A., additional, Pelosi, E., additional, Dusi, L., additional, Bulletti, C., additional, Fadini, R., additional, Lain, M., additional, Mignini Renzini, M., additional, Brambillasca, F., additional, Coticchio, G., additional, Merola, M., additional, Guglielmo, M. C., additional, Dal Canto, M., additional, Figueira, R., additional, Setti, A. S., additional, Worrilow, K. C., additional, Uzochukwu, C. 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A., additional, Perez-Garcia, L., additional, Ibanez, E., additional, Chavez, S., additional, Loewke, K., additional, Behr, B., additional, Reijo Pera, R., additional, Huang, S., additional, Wang, H., additional, Soong, Y., additional, Chang, C., additional, Okimura, T., additional, Kuwayama, M., additional, Mori, C., additional, Morita, M., additional, Uchiyama, K., additional, Aono, F., additional, Kato, K., additional, Takehara, Y., additional, Kato, O., additional, Minasi, M., additional, Casciani, V., additional, Arizzi, L., additional, Mencacci, C., additional, Piscitelli, C., additional, Cucinelli, F., additional, Tocci, A., additional, Wydooghe, E., additional, Vandaele, L., additional, Dewulf, J., additional, Van Soom, A., additional, Moon, J. H., additional, Son, W. Y., additional, Mahfoudh, A., additional, Henderson, S., additional, Jin, S. G., additional, Shalom-Paz, E., additional, Dahan, M., additional, Holzer, H., additional, Mahmoud, K., additional, Triki-Hmam, C., additional, Terras, K., additional, Hfaiedh, T., additional, Ben Aribia, M. H., additional, Otsubo, H., additional, Egashira, A., additional, Tanaka, K., additional, Matsuguma, T., additional, Murakami, M., additional, Murakami, K., additional, Otsuka, M., additional, Yoshioka, N., additional, Araki, Y., additional, Kuramoto, T., additional, Smit, J. G., additional, Sterrenburg, M. D., additional, Eijkemans, M. J. C., additional, Al-Inany, H. G., additional, Youssef, M. A. F. M., additional, Broekmans, F. J. M., additional, Willoughby, K., additional, DiPaolo, L., additional, Deys, L., additional, Lagunov, A., additional, Amin, S., additional, Faghih, M., additional, Hughes, E., additional, Karnis, M., additional, Ashkar, F., additional, King, W. A., additional, Neal, M. S., additional, Antonova, I., additional, Veleva, L., additional, Petkova, L., additional, Shterev, A., additional, Nogales, C., additional, Martinez, E., additional, Ariza, M., additional, Cernuda, D., additional, Gaytan, M., additional, Linan, A., additional, Guillen, A., additional, Bronet, F., additional, Cottin, V., additional, Fabian, D., additional, Allemann, F., additional, Koller, A., additional, Spira, J. C., additional, Agudo, D., additional, Martinez-Burgos, M., additional, Arnanz, A., additional, Basile, N., additional, Rodriguez, A., additional, Cho, Y. S., additional, Filioli Uranio, M., additional, Ambruosi, B., additional, Paternoster, M. S., additional, Totaro, P., additional, Sardanelli, A. M., additional, Dell'Aquila, M. E., additional, Zollner, U., additional, Hofmann, T., additional, Zollner, K. P., additional, Kovacic, B., additional, Roglic, P., additional, Vlaisavljevic, V., additional, Sole, M., additional, Boada, M., additional, Coroleu, B., additional, Veiga, A., additional, Martiny, G., additional, Molinari, M., additional, Revelli, A., additional, Chimote, N. M., additional, Chimote, M., additional, Mehta, B., additional, Chimote, N. N., additional, Sheikh, N., additional, Nath, N., additional, Mukherjee, A., additional, Rakic, K., additional, Reljic, M., additional, Ingerslev, H. J., additional, Kirkegaard, K., additional, Hindkjaer, J., additional, Agerholm, I., additional, Kitasaka, H., additional, Fukunaga, N., additional, Nagai, R., additional, Yoshimura, T., additional, Tamura, F., additional, Kitamura, K., additional, Hasegawa, N., additional, Nakayama, K., additional, Katou, M., additional, Itoi, F., additional, Asano, E., additional, Deguchi, N., additional, Ooyama, K., additional, Hashiba, Y., additional, Asada, Y., additional, Michaeli, M., additional, Rotfarb, N., additional, Karchovsky, E., additional, Ruzov, O., additional, Atamny, R., additional, Slush, K., additional, Fainaru, O., additional, Ellenbogen, A., additional, Chekuri, S., additional, Chaisrisawatsuk, T., additional, Chen, P., additional, Pangestu, M., additional, Jansen, S., additional, Catt, S., additional, Molinari, E., additional, Racca, C., additional, Ryu, C., additional, Kang, S., additional, Lee, J., additional, Chung, D., additional, Roh, S., additional, Chi, H., additional, Yokota, Y., additional, Yokota, M., additional, Yokota, H., additional, Sato, S., additional, Nakagawa, M., additional, Komatsubara, M., additional, Makita, M., additional, Oyama, K., additional, Naruse, K., additional, Kilani, S., additional, Chapman, M. G., additional, Kwik, M., additional, Chapman, M., additional, Guven, S., additional, Odaci, E., additional, Yildirim, O., additional, Kart, C., additional, Unsal, M. A., additional, Yulug, E., additional, Isachenko, E., additional, Maettner, R., additional, Strehler, E., additional, Isachenko, V., additional, Hancke, K., additional, Kreienberg, R., additional, Sterzik, K., additional, Zheng, X. Y., additional, Wang, L. N., additional, Liu, P., additional, Qiao, J., additional, Inoue, F., additional, Dashtizad, M., additional, Wahid, H., additional, Rosnina, Y., additional, Daliri, M., additional, Hajarian, H., additional, Akbarpour, M., additional, Abbas Mazni, O., additional, Knez, K., additional, Tomaevic, T., additional, Vrtacnik Bokal, E., additional, Zorn, B., additional, Virant Klun, I., additional, Koster, M., additional, Liebenthron, J., additional, Nicolov, A., additional, van der Ven, K., additional, van der Ven, H., additional, Montag, M., additional, Fayazi, M., additional, Salehnia, M., additional, Beigi Boroujeni, M., additional, Khansarinejad, B., additional, Deignan, K., additional, Emerson, G., additional, Mocanu, E., additional, Wang, J. J., additional, Andonov, M., additional, Linara, E., additional, Ahuja, K. K., additional, Nachef, S., additional, Pasqualotto, F. F., additional, Pasqualotto, E., additional, Chang, C. C., additional, Bernal, D. P., additional, Elliott, T. A., additional, Shapiro, D. B., additional, Toledo, A. A., additional, Economou, K., additional, Davies, S., additional, Argyrou, M., additional, Doriza, S., additional, Sisi, P., additional, Moschopoulou, M., additional, Karagianni, A., additional, Mendorou, C., additional, Polidoropoulos, N., additional, Papanicopoulos, C., additional, Stefanis, P., additional, Karamalegos, C., additional, Cazlaris, H., additional, Koutsilieris, M., additional, Mastrominas, M., additional, Gotts, S., additional, Doshi, A., additional, Harper, J., additional, Serhal, P., additional, Borini, A., additional, Guzeloglu-Kayisli, O., additional, Bianchi, V., additional, Seli, E., additional, Lappi, M., additional, Bonu, M. A., additional, Mizuta, S., additional, Hashimoto, H., additional, Kuroda, Y., additional, Matsumoto, Y., additional, Mizusawa, Y., additional, Ogata, S., additional, Yamada, S., additional, Kokeguchi, S., additional, Noda, Y., additional, Shiotani, M., additional, Stojkovic, M., additional, Ilic, M., additional, Markovic, N., additional, Stojkovic, P., additional, Feng, G., additional, Zhang, B., additional, Zhou, H., additional, Zhou, L., additional, Gan, X., additional, Qin, X., additional, Shu, J., additional, Wu, F., additional, Molina Botella, I., additional, Lazaro Ibanez, E., additional, Debon Aucejo, A., additional, Pertusa, J., additional, Fernandez Colom, P. J., additional, Li, C., additional, Zhang, Y., additional, Cui, Y., additional, Zhao, H., additional, Liu, J., additional, Oliveira, J. B. A., additional, Petersen, C. G., additional, Mauri, A. L., additional, Massaro, F. C., additional, Silva, L. F. I., additional, Ricci, J., additional, Cavagna, M., additional, Pontes, A., additional, Vagnini, L. D., additional, Baruffi, R. L. R., additional, Franco Jr., J. G., additional, Felipe, V., additional, Vilela, M., additional, Tiveron, M., additional, Lombardi, C., additional, Viglierchio, M. I., additional, Marconi, G., additional, Rawe, V., additional, Wale, P. L., additional, Gardner, D. K., additional, Nakagawa, K., additional, Sugiyama, R., additional, Nishi, Y., additional, Kuribayashi, Y., additional, Jyuen, H., additional, Yamashiro, E., additional, Shirai, A., additional, Inoue, M., additional, Hovatta, O., additional, Tohonen, V., additional, Inzunza, J., additional, Parmegiani, L., additional, Cognigni, G. E., additional, Bernardi, S., additional, Ciampaglia, W., additional, Infante, F. E., additional, Tabarelli de Fatis, C., additional, Pocognoli, P., additional, Arnone, A., additional, Maccarini, A. M., additional, Troilo, E., additional, Filicori, M., additional, Radwan, P., additional, Polac, I., additional, Borowiecka, M., additional, Bijak, M., additional, and Radwan, M., additional

Published
2011
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31. P.2.14 Clinical and electrophysiological characteristics of cardiac arrest survivors without structural heart disease

Author

Fukamizu, S., primary, Sakurada, H., additional, Yamamoto, Y., additional, Mizusawa, Y., additional, Katsuno, T., additional, Akashi, Y., additional, Yoshiga, Y., additional, Yamaguchi, H., additional, Jung-cha, O., additional, Okazaki, H., additional, Tejima, T., additional, Nishizaki, M., additional, and Hiraoka, M., additional

Published
2003
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37. Influence of meals on variations of ST segment elevation in patients with Brugada syndrome.

Author

Nishizaki M, Sakurada H, Mizusawa Y, Niki S, Hayashi T, Tanaka Y, Maeda S, Fujii H, Ashikaga T, Yamawake N, Isobe M, and Hiraoka M

Abstract

BACKGROUND: Glucose-induced insulin secretion is one of the contributing factors to fluctuation of ST segment elevation in Brugada syndrome. OBJECTIVES: The purpose of this study was to explore the influence of meals on variations of ST elevation in Brugada syndrome. METHODS: We assessed changes of ST segment elevation in lead V1-3 on ECG before and after taking meals, at midnight, and at 3:00 a.m. in 20 patients with Brugada syndrome. Plasma glucose, insulin, and K(+) concentrations were measured. Variations of ST elevation were defined as morphological changes and/or augmentation of ST segment level by >1.0 mm. RESULT: Variations of ST segment morphology or elevation level after meals were observed in 15 of 20 patients (75%). ST elevation was augmented most markedly after dinner (3.3 +/- 1.7 mm) and decreased both at midnight (2.6 +/- 1.3 mm: P < 0.01 vs after dinner) and at 3:00 a.m. (2.4 +/- 1.2 mm: P < 0.01 vs after dinner). Morphologic changes and elevation levels of ST segment were associated with changes in glucose-induced insulin levels after meals, being highest after dinner (47 +/- 33 microU/mL) and decreasing significantly at midnight (7 +/- 4 microU/mL) and at 3:00 a.m. (5 +/- 2 microU/mL). There were no correlations between ST elevation and changes in serum K(+) level or heart rate. CONCLUSIONS: The present findings suggest that variations of ST elevation are frequently associated with meals. Aggravation of ST elevation is most prominent in the evening to night after dinner rather than the period between midnight and early morning. This information may help to predict event times at high risk for life-threatening arrhythmias in Brugada syndrome. [ABSTRACT FROM AUTHOR]

Published
2008
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40. Noninvasive risk stratification of subjects with a Brugada-type electrocardiogram and no history of cardiac arrest.

Author

Ikeda T, Takami M, Sugi K, Mizusawa Y, Sakurada H, Yoshino H, Ikeda, Takanori, Takami, Mitsuaki, Sugi, Kaoru, Mizusawa, Yuka, Sakurada, Harumizu, and Yoshino, Hideaki

Abstract

Background: Recent studies suggest that the Brugada-type electrocardiogram (ECG) is much more prevalent than the manifest Brugada syndrome. Although invasive electrophysiologic investigations have been proposed as a risk stratifier, their value is controversial, and alternative noninvasive techniques may be preferred. We sought a noninvasive strategy to detect a high-risk group in a long-term follow-up study of subjects with a Brugada-type ECG, and no history of cardiac arrest.Methods: This study enrolled 124 consecutive subjects with a Brugada-type ECG. Prognostic indices included: age, sex, a family history of sudden death, syncopal episodes, a spontaneous coved-type ST-segment elevation, maximal magnitude of ST-segment elevation, a spontaneous change in ST segment, a mean QRS duration, maximal QT interval, QT dispersion, late potentials (LP) by signal-averaged ECG, and microvolt T-wave alternans.Results: Of the 124 subjects, 20 consenting subjects had an implantable defibrillator before follow-up. During a 40 +/- 19-month follow-up, 12 subjects (9.7%) reached one of the endpoints (sudden death or ventricular tachyarrhythmia). Of the 12 risk indices, a family history of sudden death, syncopal episodes, a spontaneous coved-type ST-segment elevation, a spontaneous change in ST segment, and LP had significant values. In multivariate analysis, a spontaneous change in ST segment had the most significance (a relative hazard, 9.2; P = 0.036). Combined assessment of this index and other significant indices obtained higher positive predictive values (43-71%).Conclusions: A spontaneous change in ST segment is associated with the highest risk for subsequent events in subjects with a Brugada-type ECG. The presence of syncopal episodes, a history of familial sudden death, and/or LP may increase its value. [ABSTRACT FROM AUTHOR]

Published
2005

43. New Class of Corticotropin-Releasing Factor (CRF) Antagonists:  Small Peptides Having High Binding Affinity for CRF Receptor

Author

Yamada, Y., Mizutani, K., Mizusawa, Y., Hantani, Y., Tanaka, M., Tanaka, Y., Tomimoto, M., Sugawara, M., Imai, N., Yamada, H., Okajima, N., and Haruta, J.

Abstract

The discovery of small and potent peptide antagonists of the corticotropin-releasing factor (CRF) receptor is described. Through the structure−activity relationship studies of 12-amino acid peptide corresponding to the C-terminal residues of astressin, we assumed that a particular surface of the α-helix was important for binding to the receptor. The small peptide containing d-Ala31 and cyclohexylalanine38 on that surface was as potent as astressin in binding to the CRF receptor and showed significant ACTH suppression when administered to rats.

Published
2004

49. P336 Exome sequencing of multiple affected individuals from an Irish family with Brugada Syndrome uncovers a novel locus for the disorder.

Author

Barc, J G, Marsman, RF, Le Scouarnec, S, Mizusawa, Y, Lindenbaum, P, Carter, N, Redon, R, Wilde, AAM, Mckeown, P, and Bezzina, CR

Subjects
BRUGADA syndrome, CARDIAC arrest, ELECTROCARDIOGRAPHY, FUNCTIONAL loss in older people, GENE frequency, GENE expression, CARDIOVASCULAR diseases risk factors
Abstract

Introduction: Brugada Syndrome (BrS) is a disorder associated with an increased risk of sudden cardiac death and specific ECG features consisting of ST-segment elevation in the right precordial leads. Loss-of-function mutations in SCN5A underlie the disorder in ∼25% of patients. While other genes have been implicated, these account for <1% of subjects. Thus the genetic basis of BrS remains unknown in the majority of cases. We here set out to identify the genetic defect underlying BrS in a 3 generation family from Ireland with a case of spontaneous type 1 ECG who died suddenly at 24 years old.Methods: Exome sequencing was carried out in 3 individuals from the pedigree using Agilent SureSelect Target Enrichment 50Mb capture followed by sequencing on an Illumina HiSeq 2000. These 3 individuals were selected based on their genetic distance and the presentation of a BrS ECG at baseline.Results: Comparison of 3 exomes from affected individuals identified 22,171 shared variants. Filtering out of variants occurring at a minor allele frequency (MAF) of >1% in public and in-house exome/genome databases, and considering all types of exonic variants and splice site variants, resulted in 10 rare variants shared among the 3 affected. Two of the variants are found in all afffected family members and not in the unaffected and reside in 2 different genes, namely HOOK3 and PXDNL. These 2 variants have been found at a MAF of 0.02% and 0.008%, respectively, in the NHLBI Exome Variant Project population (n=6500 individuals). The function of PXDNL, which appears to be specifically expressed in heart, is yet unknown. The PXDNL variant is predicted to be deleterious and probably damaging by SIFT and Polyphen2 algorithms, respectively.Conclusions: We identified by exome sequencing a chromosomal interval and a possible novel gene for BrS. Ongoing functional studies are aimed at investigating further the involvement of this gene in the BrS. [ABSTRACT FROM PUBLISHER]

Published
2014
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