Author: "Saarela, Anni" - Searchworks@Jio Institute Digital Library Search Results

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1. Exome sequencing reveals predominantly de novo variants in disorders with intellectual disability (ID) in the founder population of Finland

Author: Järvelä, Irma, Määttä, Tuomo, Acharya, Anushree, Leppälä, Juha, Jhangiani, Shalini N., Arvio, Maria, Siren, Auli, Kankuri-Tammilehto, Minna, Kokkonen, Hannaleena, Palomäki, Maarit, Varilo, Teppo, Fang, Mary, Hadley, Trevor D., Jolly, Angad, Linnankivi, Tarja, Paetau, Ritva, Saarela, Anni, Kälviäinen, Reetta, Olme, Jan, Nouel-Saied, Liz M., Cornejo-Sanchez, Diana M., Llaci, Lorida, Lupski, James R., Posey, Jennifer E., Leal, Suzanne M., and Schrauwen, Isabelle
Published: 2021
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2. Seizure outcome and use of antiepileptic drugs after epilepsy surgery according to histopathological diagnosis: a retrospective multicentre cohort study

Author: Aichholzer, Martin, Amorim, Isabel, Aparicio, Javier, Aronica, Eleonora, Arzimanoglou, Alexis, Barba, Carmen, Beck, Jürgen, Becker, Albert, Beckervordersandforth, Jan C, Bien, Christian G, Blümcke, Ingmar, Bodi, Istvan, Braun, Kees PJ, Catenoix, Helene, Chassoux, Francine, Chipaux, Mathilde, Cloppenborg, Thomas, Coras, Roland, Cross, J Helen, De Palma, Luca, De Tisi, Jane, Deleo, Francesco, Devaux, Bertrand, Di Gennaro, Giancarlo, Dorfmüller, Georg, Duncan, John S, Elger, Christian, Ernst, Katharina, Esposito, Vincenzo, Feucht, Martha, Gadze, Zeljka Petelin, Garbelli, Rita, Geleijns, Karin, Gil-Nagel, Antonio, Grote, Alexander, Grunwald, Thomas, Guerrini, Renzo, Hamer, Hajo, Honavar, Mrinalini, Jacques, Thomas S, Jakovcevic, Antonia, Jutila, Leena, Kalina, Adam, Kälviäinen, Reetta, Klein, Karl Martin, Koenig, Kristina, Krsek, Pavel, Kudernatsch, Manfred, Kudr, Martin, Lamberink, Herm J, Malmgren, Kristina, Marusic, Petr, Melikyan, Armen, Menzler, Katja, Noachtar, Soheyl, Otte, Willem M, Özkara, Çiğdem, Pieper, Tom, Pimentel, Jose, Raicevic, Savo, Rheims, Sylvain, Ribeiro, Joana, Rosenow, Felix, Rössler, Karl, Rydenhag, Bertil, Sales, Francisco, San Antonio-Arce, Victoria, Schaller, Karl Lothar, Schijns, Olaf, Scholl, Theresa, Schramm, Johannes, Schulze-Bonhage, Andreas, Sciot, Raf, Seeck, Margitta, Shishkina, Lyudmila, Sokic, Dragoslav, Specchio, Nicola, Theys, Tom, Thom, Maria, Delgado, Rafael Toledano, Toulouse, Joseph, Uzan, Mustafa, van Loon, Johannes, Van Paesschen, Wim, von Oertzen, Tim J, Jansen, Floor, Leijten, Frans, van Rijen, Peter, Spliet, Wim GM, Mühlebner, Angelika, Kasper, Burkhard S, Fauser, Susanne, Polster, Tilman, Kalbhenn, Thilo, Delev, Daniel, McEvoy, Andrew, Miserocchi, Anna, Landré, Elisabeth, Turak, Bares, Varlet, Pascale, Ferrand-Sorbets, Sarah, Fohlen, Martine, Bulteau, Christine, Edelvik, Anna, Shah, Mukesch J, Scheiwe, Christian, Delicado, Eva Gutierrez, Tisdall, Martin, Eltze, Christin, Akkol, Serdar, Deniz, Kaancan, Oz, Buge, Holthausen, Hans, Hartlieb, Till, Staudt, Martin, Casciato, Sara, Quarato, Pier P, Giangaspero, Felice, Streichenberger, Nathalie, Guenot, Marc, Isnard, Jean, Valentijn, Antonio, Chang, Amanda, Mullatti, Nandini, Zamecnik, Josef, Zarubova, Jana, Tomasek, Martin, Immonen, Arto, Saarela, Anni, Rauramaa, Tuomas, Lobrinus, Johannes A, Egervari, Kristof, Momjian, Shahan, Harti, Elisabeth, Lohr, Hannah, Kroell, Judith, Vermeulen, Lynn, Cleeren, Evy, Vlasov, Pavel, Kozlova, Antonia, Vorobyev, Alexey, Goeppel, Gudrun, Samueli, Sharon, Czech, Thomas, Hainfellner, Johannes, Puttinger, Gertraud, Schwarz, Gabriele, Stefanits, Harald, Weis, Serge, Spreafico, Roberto, Villani, Flavio, Rossini, Laura, Hermsen, Anke, Knake, Susanne, Nimsky, Christopher, Carl, Barbara, Belohlavkova, Anezka, Benova, Barbora, Bisschop, Jeroen, Colon, Albert, van Kranen-Mastenbroek, Vivianne, Rouhl, Rob PW, Hoogland, Govert, Rumiá, Jordi, Ramírez-Camacho, Alia, Candela-Cantó, Santiago, Ostrowsky-Coste, Karine, Panagiotakaki, Eleni, Montavont, Alexandra, Kosal, Pascale Keo, Gokce-Samar, Zeynep, Milleret, Clara, Buccoliero, Anna M, Giordano, Flavio, Sulentic, Vlatko, Mrak, Goran, Desnica, Andrej, CarfíPavia, Giusy, De Benedictis, Alessandro, Marras, Carlo E, Bascarevic, Vladimir, Vojvodic, Nikola, Ristic, Aleksandar, Rebelo, Olinda, Aledo-Serrano, Angel, Garcia-Morales, Irene, Anciones, Carla, and Braun, Kees P J
Published: 2020
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3. Novel LAMC3pathogenic variant enriched in Finnish population causes malformations of cortical development and severe epilepsy

Author: Saarela, Anni, Timonen, Oskari, Kirjavainen, Jarkko, Liu, Yawu, Silvennoinen, Katri, Mervaala, Esa, and Kälviäinen, Reetta
Abstract: Recessive LAMC3mutations are recognized to cause epilepsy with cortical malformations characterized by polymicrogyria and pachygyria. The objective of this study was to describe the clinical picture and epilepsy phenotype of four patients with a previously undescribed LAMC3variant. All epilepsy patients treated in Kuopio Epilepsy Center (located in Kuopio, Finland) are offered the possibility to participate in a scientific study investigating biomarkers in epilepsy (Epibiomarker study). We have collected a comprehensive database of the study population, and are currently re‐evaluating our database regarding the patients with developmental and/or epileptic encephalopathy (DEE). If the etiology of epilepsy remains unknown in the clinical setting, we are performing whole exome sequencing to recognize the genetic causes. Among our study population of 323 DEE patients we recognized three patients with similar homozygous LAMC3c.1866del (p.(Phe623Serfs*10)) frameshift variant and one patient with a compound heterozygous mutation where the same frameshift variant was combined with an intronic LAMC3c.4231‐12C>G variant on another allele. All these patients have severe epilepsy and either bilateral agyria‐pachygyria or bilateral polymicrogyria in their clinical MRI scanning. Cortical malformations involve the occipital lobes in all our patients. Epilepsy phenotype is variable as two of our patients have DEE with epileptic spasms progressing to Lennox–Gastaut syndrome and intellectual disability. The other two patients have focal epilepsy without marked cognitive deficit. The four patients are unrelated. LAMC3c.1866del p.(Phe623Serfs*10) frameshift variant is enriched in the Finnish population. Only a few patients with epilepsy caused by LAMC3homozygous or compound heterozygous mutations have been described in the literature. To our knowledge, the variants discovered in our patients have not previously been published. Clinical phenotype appears to be more varied than previously assumed and patients with a milder phenotype and normal cognition have probably remained unrecognized.
Published: 2024
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4. Sub-genic intolerance, ClinVar, and the epilepsies: A whole-exome sequencing study of 29,165 individuals

Author: Motelow, Joshua E., primary, Povysil, Gundula, additional, Dhindsa, Ryan S., additional, Stanley, Kate E., additional, Allen, Andrew S., additional, Feng, Yen-Chen Anne, additional, Howrigan, Daniel P., additional, Abbott, Liam E., additional, Tashman, Katherine, additional, Cerrato, Felecia, additional, Cusick, Caroline, additional, Singh, Tarjinder, additional, Heyne, Henrike, additional, Byrnes, Andrea E., additional, Churchhouse, Claire, additional, Watts, Nick, additional, Solomonson, Matthew, additional, Lal, Dennis, additional, Gupta, Namrata, additional, Neale, Benjamin M., additional, Cavalleri, Gianpiero L., additional, Cossette, Patrick, additional, Cotsapas, Chris, additional, De Jonghe, Peter, additional, Dixon-Salazar, Tracy, additional, Guerrini, Renzo, additional, Hakonarson, Hakon, additional, Heinzen, Erin L., additional, Helbig, Ingo, additional, Kwan, Patrick, additional, Marson, Anthony G., additional, Petrovski, Slavé, additional, Kamalakaran, Sitharthan, additional, Sisodiya, Sanjay M., additional, Stewart, Randy, additional, Weckhuysen, Sarah, additional, Depondt, Chantal, additional, Dlugos, Dennis J., additional, Scheffer, Ingrid E., additional, Striano, Pasquale, additional, Freyer, Catharine, additional, Krause, Roland, additional, May, Patrick, additional, McKenna, Kevin, additional, Regan, Brigid M., additional, Bennett, Caitlin A., additional, Leu, Costin, additional, Leech, Stephanie L., additional, O’Brien, Terence J., additional, Todaro, Marian, additional, Stamberger, Hannah, additional, Andrade, Danielle M., additional, Ali, Quratulain Zulfiqar, additional, Sadoway, Tara R., additional, Krestel, Heinz, additional, Schaller, André, additional, Papacostas, Savvas S., additional, Kousiappa, Ioanna, additional, Tanteles, George A., additional, Christou, Yiolanda, additional, Štěrbová, Katalin, additional, Vlčková, Markéta, additional, Sedláčková, Lucie, additional, Laššuthová, Petra, additional, Klein, Karl Martin, additional, Rosenow, Felix, additional, Reif, Philipp S., additional, Knake, Susanne, additional, Neubauer, Bernd A., additional, Zimprich, Friedrich, additional, Feucht, Martha, additional, Reinthaler, Eva M., additional, Kunz, Wolfram S., additional, Zsurka, Gábor, additional, Surges, Rainer, additional, Baumgartner, Tobias, additional, von Wrede, Randi, additional, Pendziwiat, Manuela, additional, Muhle, Hiltrud, additional, Rademacher, Annika, additional, van Baalen, Andreas, additional, von Spiczak, Sarah, additional, Stephani, Ulrich, additional, Afawi, Zaid, additional, Korczyn, Amos D., additional, Kanaan, Moien, additional, Canavati, Christina, additional, Kurlemann, Gerhard, additional, Müller-Schlüter, Karen, additional, Kluger, Gerhard, additional, Häusler, Martin, additional, Blatt, Ilan, additional, Lemke, Johannes R., additional, Krey, Ilona, additional, Weber, Yvonne G., additional, Wolking, Stefan, additional, Becker, Felicitas, additional, Lauxmann, Stephan, additional, Boßelmann, Christian, additional, Kegele, Josua, additional, Hengsbach, Christian, additional, Rau, Sarah, additional, Steinhoff, Bernhard J., additional, Schulze-Bonhage, Andreas, additional, Borggräfe, Ingo, additional, Schankin, Christoph J., additional, Schubert-Bast, Susanne, additional, Schreiber, Herbert, additional, Mayer, Thomas, additional, Korinthenberg, Rudolf, additional, Brockmann, Knut, additional, Wolff, Markus, additional, Dennig, Dieter, additional, Madeleyn, Rene, additional, Kälviäinen, Reetta, additional, Saarela, Anni, additional, Timonen, Oskari, additional, Linnankivi, Tarja, additional, Lehesjoki, Anna-Elina, additional, Rheims, Sylvain, additional, Lesca, Gaetan, additional, Ryvlin, Philippe, additional, Maillard, Louis, additional, Valton, Luc, additional, Derambure, Philippe, additional, Bartolomei, Fabrice, additional, Hirsch, Edouard, additional, Michel, Véronique, additional, Chassoux, Francine, additional, Rees, Mark I., additional, Chung, Seo-Kyung, additional, Pickrell, William O., additional, Powell, Robert, additional, Baker, Mark D., additional, Fonferko-Shadrach, Beata, additional, Lawthom, Charlotte, additional, Anderson, Joseph, additional, Schneider, Natascha, additional, Balestrini, Simona, additional, Zagaglia, Sara, additional, Braatz, Vera, additional, Johnson, Michael R., additional, Auce, Pauls, additional, Sills, Graeme J., additional, Baum, Larry W., additional, Sham, Pak C., additional, Cherny, Stacey S., additional, Lui, Colin H.T., additional, Delanty, Norman, additional, Doherty, Colin P., additional, Shukralla, Arif, additional, El-Naggar, Hany, additional, Widdess-Walsh, Peter, additional, Barišić, Nina, additional, Canafoglia, Laura, additional, Franceschetti, Silvana, additional, Castellotti, Barbara, additional, Granata, Tiziana, additional, Ragona, Francesca, additional, Zara, Federico, additional, Iacomino, Michele, additional, Riva, Antonella, additional, Madia, Francesca, additional, Vari, Maria Stella, additional, Salpietro, Vincenzo, additional, Scala, Marcello, additional, Mancardi, Maria Margherita, additional, Nobili, Lino, additional, Amadori, Elisabetta, additional, Giacomini, Thea, additional, Bisulli, Francesca, additional, Pippucci, Tommaso, additional, Licchetta, Laura, additional, Minardi, Raffaella, additional, Tinuper, Paolo, additional, Muccioli, Lorenzo, additional, Mostacci, Barbara, additional, Gambardella, Antonio, additional, Labate, Angelo, additional, Annesi, Grazia, additional, Manna, Lorella, additional, Gagliardi, Monica, additional, Parrini, Elena, additional, Mei, Davide, additional, Vetro, Annalisa, additional, Bianchini, Claudia, additional, Montomoli, Martino, additional, Doccini, Viola, additional, Barba, Carmen, additional, Hirose, Shinichi, additional, Ishii, Atsushi, additional, Suzuki, Toshimitsu, additional, Inoue, Yushi, additional, Yamakawa, Kazuhiro, additional, Beydoun, Ahmad, additional, Nasreddine, Wassim, additional, Khoueiry Zgheib, Nathalie, additional, Tumiene, Birute, additional, Utkus, Algirdas, additional, Sadleir, Lynette G., additional, King, Chontelle, additional, Caglayan, S. Hande, additional, Arslan, Mutluay, additional, Yapıcı, Zuhal, additional, Topaloglu, Pınar, additional, Kara, Bulent, additional, Yis, Uluc, additional, Turkdogan, Dilsad, additional, Gundogdu-Eken, Aslı, additional, Bebek, Nerses, additional, Uğur-İşeri, Sibel, additional, Baykan, Betül, additional, Salman, Barış, additional, Haryanyan, Garen, additional, Yücesan, Emrah, additional, Kesim, Yeşim, additional, Özkara, Çiğdem, additional, Tsai, Meng-Han, additional, Ho, Chen-Jui, additional, Lin, Chih-Hsiang, additional, Lin, Kuang-Lin, additional, Chou, I-Jun, additional, Poduri, Annapurna, additional, Shiedley, Beth R., additional, Shain, Catherine, additional, Noebels, Jeffrey L., additional, Goldman, Alicia, additional, Busch, Robyn M., additional, Jehi, Lara, additional, Najm, Imad M., additional, Ferguson, Lisa, additional, Khoury, Jean, additional, Glauser, Tracy A., additional, Clark, Peggy O., additional, Buono, Russell J., additional, Ferraro, Thomas N., additional, Sperling, Michael R., additional, Lo, Warren, additional, Privitera, Michael, additional, French, Jacqueline A., additional, Schachter, Steven, additional, Kuzniecky, Ruben I., additional, Devinsky, Orrin, additional, Hegde, Manu, additional, Greenberg, David A., additional, Ellis, Colin A., additional, Goldberg, Ethan, additional, Helbig, Katherine L., additional, Cosico, Mahgenn, additional, Vaidiswaran, Priya, additional, Fitch, Eryn, additional, Berkovic, Samuel F., additional, Lerche, Holger, additional, Lowenstein, Daniel H., additional, and Goldstein, David B., additional
Published: 2021
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5. Distinct gene-set burden patterns underlie common generalized and focal epilepsies

Author: Koko, Mahmoud, primary, Krause, Roland, additional, Sander, Thomas, additional, Bobbili, Dheeraj Reddy, additional, Nothnagel, Michael, additional, May, Patrick, additional, Lerche, Holger, additional, Feng, Yen-Chen Anne, additional, Howrigan, Daniel P, additional, Abbott, Liam E, additional, Tashman, Katherine, additional, Cerrato, Felecia, additional, Singh, Tarjinder, additional, Heyne, Henrike, additional, Byrnes, Andrea, additional, Churchhouse, Claire, additional, Watts, Nick, additional, Solomonson, Matthew, additional, Lal, Dennis, additional, Heinzen, Erin L, additional, Dhindsa, Ryan S, additional, Stanley, Kate E, additional, Cavalleri, Gianpiero L, additional, Hakonarson, Hakon, additional, Helbig, Ingo, additional, Weckhuysen, Sarah, additional, Petrovski, Slavé, additional, Kamalakaran, Sitharthan, additional, Sisodiya, Sanjay M, additional, Cossette, Patrick, additional, Cotsapas, Chris, additional, DeJonghe, Peter, additional, Dixon-Salazar, Tracy, additional, Guerrini, Renzo, additional, Kwan, Patrick, additional, Marson, Anthony G, additional, Stewart, Randy, additional, Depondt, Chantal, additional, Dlugos, Dennis J, additional, Scheffer, Ingrid E, additional, Striano, Pasquale, additional, Freyer, Catharine, additional, McKenna, Kevin, additional, Regan, Brigid M, additional, Bellows, Susannah T, additional, Leu, Costin, additional, Bennett, Caitlin A, additional, Johns, Esther M C, additional, Macdonald, Alexandra, additional, Shilling, Hannah, additional, Burgess, Rosemary, additional, Weckhuysen, Dorien, additional, Bahlo, Melanie, additional, O'Brien, Terence J, additional, Todaro, Marian, additional, Stamberger, Hannah, additional, Andrade, Danielle M, additional, Sadoway, Tara R, additional, Mo, Kelly, additional, Krestel, Heinz, additional, Gallati, Sabina, additional, Papacostas, Savvas S, additional, Kousiappa, Ioanna, additional, Tanteles, George A, additional, Štěrbová, Katalin, additional, Vlčková, Markéta, additional, Sedláčková, Lucie, additional, Laššuthová, Petra, additional, Klein, Karl Martin, additional, Rosenow, Felix, additional, Reif, Philipp S, additional, Knake, Susanne, additional, Kunz, Wolfram S, additional, Zsurka, Gábor, additional, Elger, Christian E, additional, Bauer, Jürgen, additional, Rademacher, Michael, additional, Pendziwiat, Manuela, additional, Muhle, Hiltrud, additional, Rademacher, Annika, additional, vanBaalen, Andreas, additional, vonSpiczak, Sarah, additional, Stephani, Ulrich, additional, Afawi, Zaid, additional, Korczyn, Amos D, additional, Kanaan, Moien, additional, Canavati, Christina, additional, Kurlemann, Gerhard, additional, Müller-Schlüter, Karen, additional, Kluger, Gerhard, additional, Häusler, Martin, additional, Blatt, Ilan, additional, Lemke, Johannes R, additional, Krey, Ilona, additional, Weber, Yvonne G, additional, Wolking, Stefan, additional, Becker, Felicitas, additional, Hengsbach, Christian, additional, Rau, Sarah, additional, Maisch, Ana F, additional, Steinhoff, Bernhard J, additional, Schulze-Bonhage, Andreas, additional, Schubert-Bast, Susanne, additional, Schreiber, Herbert, additional, Borggräfe, Ingo, additional, Schankin, Christoph J, additional, Mayer, Thomas, additional, Korinthenberg, Rudolf, additional, Brockmann, Knut, additional, Dennig, Dieter, additional, Madeleyn, Rene, additional, Kälviäinen, Reetta, additional, Auvinen, Pia, additional, Saarela, Anni, additional, Linnankivi, Tarja, additional, Lehesjoki, Anna-Elina, additional, Rees, Mark I, additional, Chung, Seo-Kyung, additional, Pickrell, William O, additional, Powell, Robert, additional, Schneider, Natascha, additional, Balestrini, Simona, additional, Zagaglia, Sara, additional, Braatz, Vera, additional, Johnson, Michael R, additional, Auce, Pauls, additional, Sills, Graeme J, additional, Baum, Larry W, additional, Sham, Pak C, additional, Cherny, Stacey S, additional, Lui, Colin H T, additional, Barišić, Nina, additional, Delanty, Norman, additional, Doherty, Colin P, additional, Shukralla, Arif, additional, McCormack, Mark, additional, El-Naggar, Hany, additional, Canafoglia, Laura, additional, Franceschetti, Silvana, additional, Castellotti, Barbara, additional, Granata, Tiziana, additional, Zara, Federico, additional, Iacomino, Michele, additional, Madia, Francesca, additional, Vari, Maria Stella, additional, Mancardi, Maria Margherita, additional, Salpietro, Vincenzo, additional, Bisulli, Francesca, additional, Tinuper, Paolo, additional, Licchetta, Laura, additional, Pippucci, Tommaso, additional, Stipa, Carlotta, additional, Minardi, Raffaella, additional, Gambardella, Antonio, additional, Labate, Angelo, additional, Annesi, Grazia, additional, Manna, Lorella, additional, Gagliardi, Monica, additional, Parrini, Elena, additional, Mei, Davide, additional, Vetro, Annalisa, additional, Bianchini, Claudia, additional, Montomoli, Martino, additional, Doccini, Viola, additional, Marini, Carla, additional, Suzuki, Toshimitsu, additional, Inoue, Yushi, additional, Yamakawa, Kazuhiro, additional, Tumiene, Birute, additional, Sadleir, Lynette G, additional, King, Chontelle, additional, Mountier, Emily, additional, Caglayan, Hande S, additional, Arslan, Mutluay, additional, Yapıcı, Zuhal, additional, Yis, Uluc, additional, Topaloglu, Pınar, additional, Kara, Bulent, additional, Turkdogan, Dilsad, additional, Gundogdu-Eken, Aslı, additional, Bebek, Nerses, additional, Uğur-İşeri, Sibel, additional, Baykan, Betül, additional, Salman, Barış, additional, Haryanyan, Garen, additional, Yücesan, Emrah, additional, Kesim, Yeşim, additional, Özkara, Çiğdem, additional, Poduri, Annapurna, additional, Shiedley, Beth R, additional, Shain, Catherine, additional, Buono, Russell J, additional, Ferraro, Thomas N, additional, Sperling, Michael R, additional, Lo, Warren, additional, Privitera, Michael, additional, French, Jacqueline A, additional, Schachter, Steven, additional, Kuzniecky, Ruben I, additional, Devinsky, Orrin, additional, Hegde, Manu, additional, Khankhanian, Pouya, additional, Helbig, Katherine L, additional, Ellis, Colin A, additional, Spalletta, Gianfranco, additional, Piras, Fabrizio, additional, Piras, Federica, additional, Gili, Tommaso, additional, Ciullo, Valentina, additional, Reif, Andreas, additional, McQuillin, Andrew, additional, Bass, Nick, additional, McIntosh, Andrew, additional, Blackwood, Douglas, additional, Johnstone, Mandy, additional, Palotie, Aarno, additional, Pato, Michele T, additional, Pato, Carlos N, additional, Bromet, Evelyn J, additional, Carvalho, Celia Barreto, additional, Achtyes, Eric D, additional, Azevedo, Maria Helena, additional, Kotov, Roman, additional, Lehrer, Douglas S, additional, Malaspina, Dolores, additional, Marder, Stephen R, additional, Medeiros, Helena, additional, Morley, Christopher P, additional, Perkins, Diana O, additional, Sobell, Janet L, additional, Buckley, Peter F, additional, Macciardi, Fabio, additional, Rapaport, Mark H, additional, Knowles, James A, additional, Cohort, Genomic Psychiatry, additional, Fanous, Ayman H, additional, McCarroll, Steven A, additional, Gupta, Namrata, additional, Gabriel, Stacey B, additional, Daly, Mark J, additional, Lander, Eric S, additional, Lowenstein, Daniel H, additional, Goldstein, David B, additional, Berkovic, Samuel F, additional, and Neale, Benjamin M, additional
Published: 2021
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6. Sub-genic intolerance, ClinVar, and the epilepsies: A whole-exome sequencing study of 29,165 individuals

Author: Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Motelow, Joshua E., Povysil, Gundula, Dhindsa, Ryan S., Stanley, Kate E., Allen, Andrew S., Feng, Yen-Chen Anne, Howrigan, Daniel P., Abbott, Liam E., Tashman, Katherine, Cerrato, Felecia, Cusick, Caroline, Singh, Tarjinder, Heyne, Henrike, Byrnes, Andrea E., Churchhouse, Claire, Watts, Nick, Solomonson, Matthew, Lal, Dennis, Gupta, Namrata, Neale, Benjamin M., Cavalleri, Gianpiero L., Cossette, Patrick, Cotsapas, Chris, Jonghe, Peter De, Dixon-Salazar, Tracy, Guerrini, Renzo, Hakonarson, Hakon, Heinzen, Erin L., Helbig, Ingo, Kwan, Patrick, Marson, Anthony G., Petrovski, Slavé, Kamalakaran, Sitharthan, Sisodiya, Sanjay M., Stewart, Randy, Weckhuysen, Sarah, Depondt, Chantal, Dlugos, Dennis J., Scheffer, Ingrid E., Striano, Pasquale, Freyer, Catharine, Krause, Roland, May, Patrick, McKenna, Kevin, Regan, Brigid M., Bennett, Caitlin A., Leu, Costin, Leech, Stephanie L., O’Brien, Terence J., Todaro, Marian, Stamberger, Hannah, Andrade, Danielle M., Ali, Quratulain Zulfiqar, Sadoway, Tara R., Krestel, Heinz, Schaller, André, Papacostas, Savvas S., Kousiappa, Ioanna, Tanteles, George A., Christou, Yiolanda, Štěrbová, Katalin, Vlčková, Markéta, Sedláčková, Lucie, Laššuthová, Petra, Klein, Karl Martin, Rosenow, Felix, Reif, Philipp S., Knake, Susanne, Neubauer, Bernd A., Zimprich, Friedrich, Feucht, Martha, Reinthaler, Eva M., Kunz, Wolfram S., Zsurka, Gábor, Surges, Rainer, Baumgartner, Tobias, Wrede, Randi Von, Pendziwiat, Manuela, Muhle, Hiltrud, Rademacher, Annika, Baalen, Andreas Van, Spiczak, Sarah Von, Stephani, Ulrich, Afawi, Zaid, Korczyn, Amos D., Kanaan, Moien, Canavati, Christina, Kurlemann, Gerhard, Müller-Schlüter, Karen, Kluger, Gerhard, Häusler, Martin, Blatt, Ilan, Lemke, Johannes R., Krey, Ilona, Weber, Yvonne G., Wolking, Stefan, Becker, Felicitas, Lauxmann, Stephan, Boßelmann, Christian, Kegele, Josua, Hengsbach, Christian, Rau, Sarah, Steinhoff, Bernhard J., Schulze-Bonhage, Andreas, Borggräfe, Ingo, Schankin, Christoph J., Schubert-Bast, Susanne, Schreiber, Herbert, Mayer, Thomas, Korinthenberg, Rudolf, Brockmann, Knut, Wolff, Markus, Dennig, Dieter, Madeleyn, Rene, Kälviäinen, Reetta, Saarela, Anni, Timonen, Oskari, Linnankivi, Tarja, Lehesjoki, Anna-Elina, Rheims, Sylvain, Lesca, Gaetan, Ryvlin, Philippe, Maillard, Louis, Valton, Luc, Derambure, Philippe, Bartolomei, Fabrice, Hirsch, Edouard, Michel, Véronique, Chassoux, Francine, Rees, Mark I., Chung, Seo-Kyung, Pickrell, William O., Powell, Robert, Baker, Mark D., Fonferko-Shadrach, Beata, Lawthom, Charlotte, Anderson, Joseph, Schneider, Natascha, Balestrini, Simona, Zagaglia, Sara, Braatz, Vera, Johnson, Michael R., Auce, Pauls, Sills, Graeme J., Baum, Larry W., Sham, Pak C., Cherny, Stacey S., Lui, Colin H. T., Delanty, Norman, Doherty, Colin P., Shukralla, Arif, El-Naggar, Hany, Widdess-Walsh, Peter, Barišić, Nina, Canafoglia, Laura, Franceschetti, Silvana, Castellotti, Barbara, Granata, Tiziana, Ragona, Francesca, Zara, Federico, Iacomino, Michele, Riva, Antonella, Madia, Francesca, Vari, Maria Stella, Salpietro, Vincenzo, Scala, Marcello, Mancardi, Maria Margherita, Nobili, Lino, Amadori, Elisabetta, Giacomini, Thea, Bisulli, Francesca, Pippucci, Tommaso, Licchetta, Laura, Minardi, Raffaella, Tinuper, Paolo, Muccioli, Lorenzo, Mostacci, Barbara, Gambardella, Antonio, Labate, Angelo, Annesi, Grazia, Manna, Lorella, Gagliardi, Monica, Parrini, Elena, Mei, Davide, Vetro, Annalisa, Bianchini, Claudia, Montomoli, Martino, Doccini, Viola, Barba, Carmen, Hirose, Shinichi, Ishii, Atsushi, Suzuki, Toshimitsu, Inoue, Yushi, Yamakawa, Kazuhiro, Beydoun, Ahmad, Nasreddine, Wassim, Zgheib, Nathalie Khoueiry, Tumiene, Birute, Utkus, Algirdas, Sadleir, Lynette G., King, Chontelle, Caglayan, S. Hande, Arslan, Mutluay, Yapıcı, Zuhal, Topaloglu, Pınar, Kara, Bulent, Yis, Uluc, Turkdogan, Dilsad, Gundogdu-Eken, Aslı, Bebek, Nerses, Tsai, Meng-Han, Ho, Chen-Jui, Lin, Chih-Hsiang, Lin, Kuang-Lin, Chou, I.-Jun, Poduri, Annapurna, Shiedley, Beth R., Shain, Catherine, Noebels, Jeffrey L., Goldman, Alicia, Busch, Robyn M., Jehi, Lara, Najm, Imad M., Ferguson, Lisa, Khoury, Jean, Glauser, Tracy A., Clark, Peggy O., Buono, Russell J., Ferraro, Thomas N., Sperling, Michael R., Lo, Warren, Privitera, Michael, French, Jacqueline A., Schachter, Steven, Kuzniecky, Ruben I., Devinsky, Orrin, Hegde, Manu, Greenberg, David A., Ellis, Colin A., Goldberg, Ethan, Helbig, Katherine L., Cosico, Mahgenn, Vaidiswaran, Priya, Fitch, Eryn, Berkovic, Samuel F., Lerche, Holger, Lowenstein, Daniel H., Goldstein, David B., Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Motelow, Joshua E., Povysil, Gundula, Dhindsa, Ryan S., Stanley, Kate E., Allen, Andrew S., Feng, Yen-Chen Anne, Howrigan, Daniel P., Abbott, Liam E., Tashman, Katherine, Cerrato, Felecia, Cusick, Caroline, Singh, Tarjinder, Heyne, Henrike, Byrnes, Andrea E., Churchhouse, Claire, Watts, Nick, Solomonson, Matthew, Lal, Dennis, Gupta, Namrata, Neale, Benjamin M., Cavalleri, Gianpiero L., Cossette, Patrick, Cotsapas, Chris, Jonghe, Peter De, Dixon-Salazar, Tracy, Guerrini, Renzo, Hakonarson, Hakon, Heinzen, Erin L., Helbig, Ingo, Kwan, Patrick, Marson, Anthony G., Petrovski, Slavé, Kamalakaran, Sitharthan, Sisodiya, Sanjay M., Stewart, Randy, Weckhuysen, Sarah, Depondt, Chantal, Dlugos, Dennis J., Scheffer, Ingrid E., Striano, Pasquale, Freyer, Catharine, Krause, Roland, May, Patrick, McKenna, Kevin, Regan, Brigid M., Bennett, Caitlin A., Leu, Costin, Leech, Stephanie L., O’Brien, Terence J., Todaro, Marian, Stamberger, Hannah, Andrade, Danielle M., Ali, Quratulain Zulfiqar, Sadoway, Tara R., Krestel, Heinz, Schaller, André, Papacostas, Savvas S., Kousiappa, Ioanna, Tanteles, George A., Christou, Yiolanda, Štěrbová, Katalin, Vlčková, Markéta, Sedláčková, Lucie, Laššuthová, Petra, Klein, Karl Martin, Rosenow, Felix, Reif, Philipp S., Knake, Susanne, Neubauer, Bernd A., Zimprich, Friedrich, Feucht, Martha, Reinthaler, Eva M., Kunz, Wolfram S., Zsurka, Gábor, Surges, Rainer, Baumgartner, Tobias, Wrede, Randi Von, Pendziwiat, Manuela, Muhle, Hiltrud, Rademacher, Annika, Baalen, Andreas Van, Spiczak, Sarah Von, Stephani, Ulrich, Afawi, Zaid, Korczyn, Amos D., Kanaan, Moien, Canavati, Christina, Kurlemann, Gerhard, Müller-Schlüter, Karen, Kluger, Gerhard, Häusler, Martin, Blatt, Ilan, Lemke, Johannes R., Krey, Ilona, Weber, Yvonne G., Wolking, Stefan, Becker, Felicitas, Lauxmann, Stephan, Boßelmann, Christian, Kegele, Josua, Hengsbach, Christian, Rau, Sarah, Steinhoff, Bernhard J., Schulze-Bonhage, Andreas, Borggräfe, Ingo, Schankin, Christoph J., Schubert-Bast, Susanne, Schreiber, Herbert, Mayer, Thomas, Korinthenberg, Rudolf, Brockmann, Knut, Wolff, Markus, Dennig, Dieter, Madeleyn, Rene, Kälviäinen, Reetta, Saarela, Anni, Timonen, Oskari, Linnankivi, Tarja, Lehesjoki, Anna-Elina, Rheims, Sylvain, Lesca, Gaetan, Ryvlin, Philippe, Maillard, Louis, Valton, Luc, Derambure, Philippe, Bartolomei, Fabrice, Hirsch, Edouard, Michel, Véronique, Chassoux, Francine, Rees, Mark I., Chung, Seo-Kyung, Pickrell, William O., Powell, Robert, Baker, Mark D., Fonferko-Shadrach, Beata, Lawthom, Charlotte, Anderson, Joseph, Schneider, Natascha, Balestrini, Simona, Zagaglia, Sara, Braatz, Vera, Johnson, Michael R., Auce, Pauls, Sills, Graeme J., Baum, Larry W., Sham, Pak C., Cherny, Stacey S., Lui, Colin H. T., Delanty, Norman, Doherty, Colin P., Shukralla, Arif, El-Naggar, Hany, Widdess-Walsh, Peter, Barišić, Nina, Canafoglia, Laura, Franceschetti, Silvana, Castellotti, Barbara, Granata, Tiziana, Ragona, Francesca, Zara, Federico, Iacomino, Michele, Riva, Antonella, Madia, Francesca, Vari, Maria Stella, Salpietro, Vincenzo, Scala, Marcello, Mancardi, Maria Margherita, Nobili, Lino, Amadori, Elisabetta, Giacomini, Thea, Bisulli, Francesca, Pippucci, Tommaso, Licchetta, Laura, Minardi, Raffaella, Tinuper, Paolo, Muccioli, Lorenzo, Mostacci, Barbara, Gambardella, Antonio, Labate, Angelo, Annesi, Grazia, Manna, Lorella, Gagliardi, Monica, Parrini, Elena, Mei, Davide, Vetro, Annalisa, Bianchini, Claudia, Montomoli, Martino, Doccini, Viola, Barba, Carmen, Hirose, Shinichi, Ishii, Atsushi, Suzuki, Toshimitsu, Inoue, Yushi, Yamakawa, Kazuhiro, Beydoun, Ahmad, Nasreddine, Wassim, Zgheib, Nathalie Khoueiry, Tumiene, Birute, Utkus, Algirdas, Sadleir, Lynette G., King, Chontelle, Caglayan, S. Hande, Arslan, Mutluay, Yapıcı, Zuhal, Topaloglu, Pınar, Kara, Bulent, Yis, Uluc, Turkdogan, Dilsad, Gundogdu-Eken, Aslı, Bebek, Nerses, Tsai, Meng-Han, Ho, Chen-Jui, Lin, Chih-Hsiang, Lin, Kuang-Lin, Chou, I.-Jun, Poduri, Annapurna, Shiedley, Beth R., Shain, Catherine, Noebels, Jeffrey L., Goldman, Alicia, Busch, Robyn M., Jehi, Lara, Najm, Imad M., Ferguson, Lisa, Khoury, Jean, Glauser, Tracy A., Clark, Peggy O., Buono, Russell J., Ferraro, Thomas N., Sperling, Michael R., Lo, Warren, Privitera, Michael, French, Jacqueline A., Schachter, Steven, Kuzniecky, Ruben I., Devinsky, Orrin, Hegde, Manu, Greenberg, David A., Ellis, Colin A., Goldberg, Ethan, Helbig, Katherine L., Cosico, Mahgenn, Vaidiswaran, Priya, Fitch, Eryn, Berkovic, Samuel F., Lerche, Holger, Lowenstein, Daniel H., and Goldstein, David B.
Abstract: Summary Both mild and severe epilepsies are influenced by variants in the same genes, yet an explanation for the resulting phenotypic variation is unknown. As part of the ongoing Epi25 Collaboration, we performed a whole-exome sequencing analysis of 13,487 epilepsy-affected individuals and 15,678 control individuals. While prior Epi25 studies focused on gene-based collapsing analyses, we asked how the pattern of variation within genes differs by epilepsy type. Specifically, we compared the genetic architectures of severe developmental and epileptic encephalopathies (DEEs) and two generally less severe epilepsies, genetic generalized epilepsy and non-acquired focal epilepsy (NAFE). Our gene-based rare variant collapsing analysis used geographic ancestry-based clustering that included broader ancestries than previously possible and revealed novel associations. Using the missense intolerance ratio (MTR), we found that variants in DEE-affected individuals are in significantly more intolerant genic sub-regions than those in NAFE-affected individuals. Only previously reported pathogenic variants absent in available genomic datasets showed a significant burden in epilepsy-affected individuals compared with control individuals, and the ultra-rare pathogenic variants associated with DEE were located in more intolerant genic sub-regions than variants associated with non-DEE epilepsies. MTR filtering improved the yield of ultra-rare pathogenic variants in affected individuals compared with control individuals. Finally, analysis of variants in genes without a disease association revealed a significant burden of loss-of-function variants in the genes most intolerant to such variation, indicating additional epilepsy-risk genes yet to be discovered. Taken together, our study suggests that genic and sub-genic intolerance are critical characteristics for interpreting the effects of variation in genes that influence epilepsy.
Published: 2021

7. Epilepsy Subtype-Specific Copy Number Burden Observed in a Genome-Wide Study of 17 458 Subjects

Author: Niestroj, Lisa-Marie, Perez-Palma, Eduardo, Howrigan, Daniel P., Zhou, Yadi, Cheng, Feixiong, Saarentaus, Elmo, Nürnberg, Peter, Stevelink, Remi, Daly, Mark J., Palotie, Aarno, Lal, Dennis, Feng, Yen-Chen Anne, Abbott, Liam E., Tashman, Katherine, Cerrato, Felecia, Churchhouse, Claire, Gupta, Namrata, Neale, Benjamin M., Berkovic, Samuel F., Lerche, Holger, Goldstein, David B., Lowenstein, Daniel H., Cavalleri, Gianpiero L., Cossette, Patrick, Cotsapas, Chris, Dixon-Salazar, Tracy, Guerrini, Renzo, Hakonarson, Hakon, Heinzen, Erin L., Helbig, Ingo, Kwan, Patrick, Marson, Anthony G., Petrovski, Slavé, Kamalakaran, Sitharthan, Sisodiya, Sanjay M., Stewart, Randy, Depondt, Chantal, Dlugos, Dennis J., Scheffer, Ingrid E., Striano, Pasquale, Freyer, Catharine, Krause, Roland, May, Patrick, McKenna, Kevin, Regan, Brigid M., Bellows, Susannah T., Leu, Costin, Bennett, Caitlin A., Johns, Esther C., Macdonald, Alexandra, Shilling, Hannah, Burgess, Rosemary, Weckhuysen, Dorien, Bahlo, Melanie, O’Brien, Terence J., Todaro, Marian, Weckhuysen, Sarah, Stamberger, Hannah, De Jonghe, Peter, Andrade, Danielle M., Sadoway, Tara R., Mo, Kelly, Krestel, Heinz, Gallati, Sabina, Papacostas, Savvas S., Kousiappa, Ioanna, Tanteles, George A., Šterbová, Katalin, Vlcková, Markéta, Sedlácková, Lucie, Laššuthová, Petra, Klein, Karl Martin, Rosenow, Felix, Reif, Philipp S., Knake, Susanne, Kunz, Wolfram S., Zsurka, Gábor, Elger, Christian E., Bauer, Jürgen, Rademacher, Michael, Pendziwiat, Manuela, Muhle, Hiltrud, Rademacher, Annika, van Baalen, Andreas, von Spiczak, Sarah, Stephani, Ulrich, Afawi, Zaid, Korczyn, Amos D., Kanaan, Moien, Canavati, Christina, Kurlemann, Gerhard, Müller-Schlüter, Karen, Kluger, Gerhard, Häusler, Martin, Blatt, Ilan, Lemke, Johannes R., Krey, Ilona, Weber, Yvonne G., Wolking, Stefan, Becker, Felicitas, Hengsbach, Christian, Rau, Sarah, Maisch, Ana F., Steinhoff, Bernhard J., Schulze-Bonhage, Andreas, Schubert-Bast, Susanne, Schreiber, Herbert, Borggräfe, Ingo, Schankin, Christoph J., Mayer, Thomas, Korinthenberg, Rudolf, Brockmann, Knut, Dennig, Dieter, Madeleyn, Rene, Kälviäinen, Reetta, Auvinen, Pia, Saarela, Anni, Linnankivi, Tarja, Lehesjoki, Anna-Elina, Rees, Mark I., Chung, Seo-Kyung, Pickrell, William O., Powell, Robert, Schneider, Natascha, Balestrini, Simona, Zagaglia, Sara, Braatz, Vera, Johnson, Michael R., Auce, Pauls, Sills, Graeme J., Baum, Larry W., Sham, Pak C., Cherny, Stacey S., Lui, Colin H. T., Barišic, Nina, Delanty, Norman, Doherty, Colin P., Shukralla, Arif, McCormack, Mark, El-Naggar, Hany, Canafoglia, Laura, Franceschetti, Silvana, Castellotti, Barbara, Granata, Tiziana, Zara, Federico, Iacomino, Michele, Madia, Francesca, Vari, Maria Stella, Mancardi, Maria Margherita, Salpietro, Vincenzo, Bisulli, Francesca, Tinuper, Paolo, Licchetta, Laura, Pippucci, Tommaso, Stipa, Carlotta, Muccioli, Lorenzo, Minardi, Raffaella, Gambardella, Antonio, Labate, Angelo, Annesi, Grazia, Manna, Lorella, Gagliardi, Monica, Parrini, Elena, Mei, Davide, Vetro, Annalisa, Bianchini, Claudia, Montomoli, Martino, Doccini, Viola, Marini, Carla, Suzuki, Toshimitsu, Inoue, Yushi, Yamakawa, Kazuhiro, Tumiene, Birute, Mameniskiene, Ruta, Utkus, Algirdas, Praninskiene, Ruta, Grikiniene, Jurgita, Samaitiene, Ruta, Sadleir, Lynette G., King, Chontelle, Mountier, Emily, Caglayan, S. Hande, Arslan, Mutluay, Yapici, Zuhal, Yis, Uluc, Topaloglu, Pinar, Kara, Bulent, Turkdogan, Dilsad, Gundogdu-Eken, Asli, Bebek, Nerses, Ugur-Iseri, Sibel, Baykan, Betül, Salman, Baris, Haryanyan, Garen, Yücesan, Emrah, Kesim, Yesim, Özkara, Çigdem, Sheidley, Beth R., Shain, Catherine, Poduri, Annapurna, Buono, Russell J, Ferraro, Thomas N, Sperling, Michael R., Lo, Warren, Privitera, Michael, French, Jacqueline A., Schachter, Steven, Kuzniecky, Ruben I., Devinsky, Orrin, Hegde, Manu, Khankhanian, Pouya, Helbig, Katherine L., Ellis, Colin A., Spalletta, Gianfranco, Piras, Fabrizio, Piras, Federica, Gili, Tommaso, Ciullo, Valentina, YÜCESAN, EMRAH, Niestroj L.-M., Perez-Palma E., Howrigan D.P., Zhou Y., Cheng F., Saarentaus E., Nurnberg P., Stevelink R., Daly M.J., Palotie A., Lal D, Epi 25 Collaborative, Bisulli F., Tinuper P., Licchetta L., and Epi25 Collaborative
Subjects: Developmental and epileptic encephalopathy, Male, 0301 basic medicine, DNA Copy Number Variations, Disease, Bioinformatics, Genome, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, copy number variation, developmental and epileptic encephalopathy, epilepsy, focal epilepsy, genetic generalized epilepsy, medicine, Humans, Genetic Predisposition to Disease, Copy-number variation, Generalized epilepsy, DNA Copy Number Variation, Copy number variation, business.industry, Breakpoint, Focal epilepsy, Original Articles, medicine.disease, 3. Good health, Genetic generalized epilepsy, 030104 developmental biology, Female, Human medicine, Neurology (clinical), Personalized medicine, business, 030217 neurology & neurosurgery, Genome-Wide Association Study, Human
Abstract: Cytogenic testing is routinely applied in most neurological centres for severe paediatric epilepsies. However, which characteristics of copy number variants (CNVs) confer most epilepsy risk and which epilepsy subtypes carry the most CNV burden, have not been explored on a genome-wide scale. Here, we present the largest CNV investigation in epilepsy to date with 10 712 European epilepsy cases and 6746 ancestry-matched controls. Patients with genetic generalized epilepsy, lesional focal epilepsy, non-acquired focal epilepsy, and developmental and epileptic encephalopathy were included. All samples were processed with the same technology and analysis pipeline. All investigated epilepsy types, including lesional focal epilepsy patients, showed an increase in CNV burden in at least one tested category compared to controls. However, we observed striking differences in CNV burden across epilepsy types and investigated CNV categories. Genetic generalized epilepsy patients have the highest CNV burden in all categories tested, followed by developmental and epileptic encephalopathy patients. Both epilepsy types also show association for deletions covering genes intolerant for truncating variants. Genome-wide CNV breakpoint association showed not only significant loci for genetic generalized and developmental and epileptic encephalopathy patients but also for lesional focal epilepsy patients. With a 34-fold risk for developing genetic generalized epilepsy, we show for the first time that the established epilepsy-associated 15q13.3 deletion represents the strongest risk CNV for genetic generalized epilepsy across the whole genome. Using the human interactome, we examined the largest connected component of the genes overlapped by CNVs in the four epilepsy types. We observed that genetic generalized epilepsy and non-acquired focal epilepsy formed disease modules. In summary, we show that in all common epilepsy types, 1.5–3% of patients carry epilepsy-associated CNVs. The characteristics of risk CNVs vary tremendously across and within epilepsy types. Thus, we advocate genome-wide genomic testing to identify all disease-associated types of CNVs.
Published: 2020
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8. Seizure outcome and use of antiepileptic drugs after epilepsy surgery according to histopathological diagnosis: a retrospective multicentre cohort study

Author: Lamberink, Herm J, primary, Otte, Willem M, additional, Blümcke, Ingmar, additional, Braun, Kees P J, additional, Aichholzer, Martin, additional, Amorim, Isabel, additional, Aparicio, Javier, additional, Aronica, Eleonora, additional, Arzimanoglou, Alexis, additional, Barba, Carmen, additional, Beck, Jürgen, additional, Becker, Albert, additional, Beckervordersandforth, Jan C, additional, Bien, Christian G, additional, Bodi, Istvan, additional, Braun, Kees PJ, additional, Catenoix, Helene, additional, Chassoux, Francine, additional, Chipaux, Mathilde, additional, Cloppenborg, Thomas, additional, Coras, Roland, additional, Cross, J Helen, additional, De Palma, Luca, additional, De Tisi, Jane, additional, Deleo, Francesco, additional, Devaux, Bertrand, additional, Di Gennaro, Giancarlo, additional, Dorfmüller, Georg, additional, Duncan, John S, additional, Elger, Christian, additional, Ernst, Katharina, additional, Esposito, Vincenzo, additional, Feucht, Martha, additional, Gadze, Zeljka Petelin, additional, Garbelli, Rita, additional, Geleijns, Karin, additional, Gil-Nagel, Antonio, additional, Grote, Alexander, additional, Grunwald, Thomas, additional, Guerrini, Renzo, additional, Hamer, Hajo, additional, Honavar, Mrinalini, additional, Jacques, Thomas S, additional, Jakovcevic, Antonia, additional, Jutila, Leena, additional, Kalina, Adam, additional, Kälviäinen, Reetta, additional, Klein, Karl Martin, additional, Koenig, Kristina, additional, Krsek, Pavel, additional, Kudernatsch, Manfred, additional, Kudr, Martin, additional, Lamberink, Herm J, additional, Malmgren, Kristina, additional, Marusic, Petr, additional, Melikyan, Armen, additional, Menzler, Katja, additional, Noachtar, Soheyl, additional, Özkara, Çiğdem, additional, Pieper, Tom, additional, Pimentel, Jose, additional, Raicevic, Savo, additional, Rheims, Sylvain, additional, Ribeiro, Joana, additional, Rosenow, Felix, additional, Rössler, Karl, additional, Rydenhag, Bertil, additional, Sales, Francisco, additional, San Antonio-Arce, Victoria, additional, Schaller, Karl Lothar, additional, Schijns, Olaf, additional, Scholl, Theresa, additional, Schramm, Johannes, additional, Schulze-Bonhage, Andreas, additional, Sciot, Raf, additional, Seeck, Margitta, additional, Shishkina, Lyudmila, additional, Sokic, Dragoslav, additional, Specchio, Nicola, additional, Theys, Tom, additional, Thom, Maria, additional, Delgado, Rafael Toledano, additional, Toulouse, Joseph, additional, Uzan, Mustafa, additional, van Loon, Johannes, additional, Van Paesschen, Wim, additional, von Oertzen, Tim J, additional, Jansen, Floor, additional, Leijten, Frans, additional, van Rijen, Peter, additional, Spliet, Wim GM, additional, Mühlebner, Angelika, additional, Kasper, Burkhard S, additional, Fauser, Susanne, additional, Polster, Tilman, additional, Kalbhenn, Thilo, additional, Delev, Daniel, additional, McEvoy, Andrew, additional, Miserocchi, Anna, additional, Landré, Elisabeth, additional, Turak, Bares, additional, Varlet, Pascale, additional, Ferrand-Sorbets, Sarah, additional, Fohlen, Martine, additional, Bulteau, Christine, additional, Edelvik, Anna, additional, Shah, Mukesch J, additional, Scheiwe, Christian, additional, Delicado, Eva Gutierrez, additional, Tisdall, Martin, additional, Eltze, Christin, additional, Akkol, Serdar, additional, Deniz, Kaancan, additional, Oz, Buge, additional, Holthausen, Hans, additional, Hartlieb, Till, additional, Staudt, Martin, additional, Casciato, Sara, additional, Quarato, Pier P, additional, Giangaspero, Felice, additional, Streichenberger, Nathalie, additional, Guenot, Marc, additional, Isnard, Jean, additional, Valentijn, Antonio, additional, Chang, Amanda, additional, Mullatti, Nandini, additional, Zamecnik, Josef, additional, Zarubova, Jana, additional, Tomasek, Martin, additional, Immonen, Arto, additional, Saarela, Anni, additional, Rauramaa, Tuomas, additional, Lobrinus, Johannes A, additional, Egervari, Kristof, additional, Momjian, Shahan, additional, Harti, Elisabeth, additional, Lohr, Hannah, additional, Kroell, Judith, additional, Vermeulen, Lynn, additional, Cleeren, Evy, additional, Vlasov, Pavel, additional, Kozlova, Antonia, additional, Vorobyev, Alexey, additional, Goeppel, Gudrun, additional, Samueli, Sharon, additional, Czech, Thomas, additional, Hainfellner, Johannes, additional, Puttinger, Gertraud, additional, Schwarz, Gabriele, additional, Stefanits, Harald, additional, Weis, Serge, additional, Spreafico, Roberto, additional, Villani, Flavio, additional, Rossini, Laura, additional, Hermsen, Anke, additional, Knake, Susanne, additional, Nimsky, Christopher, additional, Carl, Barbara, additional, Belohlavkova, Anezka, additional, Benova, Barbora, additional, Bisschop, Jeroen, additional, Colon, Albert, additional, van Kranen-Mastenbroek, Vivianne, additional, Rouhl, Rob PW, additional, Hoogland, Govert, additional, Rumiá, Jordi, additional, Ramírez-Camacho, Alia, additional, Candela-Cantó, Santiago, additional, Ostrowsky-Coste, Karine, additional, Panagiotakaki, Eleni, additional, Montavont, Alexandra, additional, Kosal, Pascale Keo, additional, Gokce-Samar, Zeynep, additional, Milleret, Clara, additional, Buccoliero, Anna M, additional, Giordano, Flavio, additional, Sulentic, Vlatko, additional, Mrak, Goran, additional, Desnica, Andrej, additional, CarfíPavia, Giusy, additional, De Benedictis, Alessandro, additional, Marras, Carlo E, additional, Bascarevic, Vladimir, additional, Vojvodic, Nikola, additional, Ristic, Aleksandar, additional, Rebelo, Olinda, additional, Aledo-Serrano, Angel, additional, Garcia-Morales, Irene, additional, and Anciones, Carla, additional
Published: 2020
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9. Ultra-Rare Genetic Variation in the Epilepsies: A Whole-Exome Sequencing Study of 17,606 Individuals

Author: Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Feng, Yen-Chen Anne, Howrigan, Daniel P., Abbott, Liam E., Tashman, Katherine, Cerrato, Felecia, Singh, Tarjinder, Heyne, Henrike, Byrnes, Andrea, Churchhouse, Claire, Watts, Nick, Solomonson, Matthew, Lal, Dennis, Heinzen, Erin L., Dhindsa, Ryan S., Stanley, Kate E., Cavalleri, Gianpiero L., Hakonarson, Hakon, Helbig, Ingo, Krause, Roland, May, Patrick, Weckhuysen, Sarah, Petrovski, Slavé, Kamalakaran, Sitharthan, Sisodiya, Sanjay M., Cossette, Patrick, Cotsapas, Chris, Jonghe, Peter De, Dixon-Salazar, Tracy, Guerrini, Renzo, Kwan, Patrick, Marson, Anthony G., Stewart, Randy, Depondt, Chantal, Dlugos, Dennis J., Scheffer, Ingrid E., Striano, Pasquale, Freyer, Catharine, McKenna, Kevin, Regan, Brigid M., Bellows, Susannah T., Leu, Costin, Bennett, Caitlin A., Johns, Esther M. C., Macdonald, Alexandra, Shilling, Hannah, Burgess, Rosemary, Weckhuysen, Dorien, Bahlo, Melanie, O’Brien, Terence J., Todaro, Marian, Stamberger, Hannah, Andrade, Danielle M., Sadoway, Tara R., Mo, Kelly, Krestel, Heinz, Gallati, Sabina, Papacostas, Savvas S., Kousiappa, Ioanna, Tanteles, George A., Štěrbová, Katalin, Vlčková, Markéta, Sedláčková, Lucie, Laššuthová, Petra, Klein, Karl Martin, Rosenow, Felix, Reif, Philipp S., Knake, Susanne, Kunz, Wolfram S., Zsurka, Gábor, Elger, Christian E., Bauer, Jürgen, Rademacher, Michael, Pendziwiat, Manuela, Muhle, Hiltrud, Rademacher, Annika, Baalen, Andreas Van, Spiczak, Sarah Von, Stephani, Ulrich, Afawi, Zaid, Korczyn, Amos D., Kanaan, Moien, Canavati, Christina, Kurlemann, Gerhard, Müller-Schlüter, Karen, Kluger, Gerhard, Häusler, Martin, Blatt, Ilan, Lemke, Johannes R., Krey, Ilona, Weber, Yvonne G., Wolking, Stefan, Becker, Felicitas, Hengsbach, Christian, Rau, Sarah, Maisch, Ana F., Steinhoff, Bernhard J., Schulze-Bonhage, Andreas, Schubert-Bast, Susanne, Schreiber, Herbert, Borggräfe, Ingo, Schankin, Christoph J., Mayer, Thomas, Korinthenberg, Rudolf, Brockmann, Knut, Dennig, Dieter, Madeleyn, Rene, Kälviäinen, Reetta, Auvinen, Pia, Saarela, Anni, Linnankivi, Tarja, Lehesjoki, Anna-Elina, Rees, Mark I., Chung, Seo-Kyung, Pickrell, William O., Powell, Robert, Schneider, Natascha, Balestrini, Simona, Zagaglia, Sara, Braatz, Vera, Johnson, Michael R., Auce, Pauls, Sills, Graeme J., Baum, Larry W., Sham, Pak C., Cherny, Stacey S., Lui, Colin H. T., Barišić, Nina, Delanty, Norman, Doherty, Colin P., Shukralla, Arif, McCormack, Mark, El-Naggar, Hany, Canafoglia, Laura, Franceschetti, Silvana, Castellotti, Barbara, Granata, Tiziana, Zara, Federico, Iacomino, Michele, Madia, Francesca, Vari, Maria Stella, Mancardi, Maria Margherita, Salpietro, Vincenzo, Bisulli, Francesca, Tinuper, Paolo, Licchetta, Laura, Pippucci, Tommaso, Stipa, Carlotta, Minardi, Raffaella, Gambardella, Antonio, Labate, Angelo, Annesi, Grazia, Manna, Lorella, Gagliardi, Monica, Parrini, Elena, Mei, Davide, Vetro, Annalisa, Bianchini, Claudia, Montomoli, Martino, Doccini, Viola, Marini, Carla, Suzuki, Toshimitsu, Inoue, Yushi, Yamakawa, Kazuhiro, Tumiene, Birute, Sadleir, Lynette G., King, Chontelle, Mountier, Emily, Caglayan, S. Hande, Arslan, Mutluay, Yapıcı, Zuhal, Yis, Uluc, Topaloglu, Pınar, Kara, Bulent, Turkdogan, Dilsad, Gundogdu-Eken, Aslı, Bebek, Nerses, Uğur-İşeri, Sibel, Baykan, Betül, Salman, Barış, Haryanyan, Garen, Yücesan, Emrah, Kesim, Yeşim, Özkara, Çiğdem, Poduri, Annapurna, Shiedley, Beth R., Shain, Catherine, Buono, Russell J., Ferraro, Thomas N., Sperling, Michael R., Lo, Warren, Privitera, Michael, French, Jacqueline A., Schachter, Steven, Kuzniecky, Ruben I., Devinsky, Orrin, Hegde, Manu, Khankhanian, Pouya, Helbig, Katherine L., Ellis, Colin A., Spalletta, Gianfranco, Piras, Fabrizio, Piras, Federica, Gili, Tommaso, Ciullo, Valentina, Reif, Andreas, McQuillin, Andrew, Bass, Nick, McIntosh, Andrew, Blackwood, Douglas, Johnstone, Mandy, Palotie, Aarno, Pato, Michele T., Pato, Carlos N., Bromet, Evelyn J., Carvalho, Celia Barreto, Achtyes, Eric D., Azevedo, Maria Helena, Kotov, Roman, Lehrer, Douglas S., Malaspina, Dolores, Marder, Stephen R., Medeiros, Helena, Morley, Christopher P., Perkins, Diana O., Sobell, Janet L., Buckley, Peter F., Macciardi, Fabio, Rapaport, Mark H., Knowles, James A., Fanous, Ayman H., McCarroll, Steven A., Gupta, Namrata, Gabriel, Stacey B., Daly, Mark J., Lander, Eric S., Lowenstein, Daniel H., Goldstein, David B., Lerche, Holger, Berkovic, Samuel F., Neale, Benjamin M., Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Feng, Yen-Chen Anne, Howrigan, Daniel P., Abbott, Liam E., Tashman, Katherine, Cerrato, Felecia, Singh, Tarjinder, Heyne, Henrike, Byrnes, Andrea, Churchhouse, Claire, Watts, Nick, Solomonson, Matthew, Lal, Dennis, Heinzen, Erin L., Dhindsa, Ryan S., Stanley, Kate E., Cavalleri, Gianpiero L., Hakonarson, Hakon, Helbig, Ingo, Krause, Roland, May, Patrick, Weckhuysen, Sarah, Petrovski, Slavé, Kamalakaran, Sitharthan, Sisodiya, Sanjay M., Cossette, Patrick, Cotsapas, Chris, Jonghe, Peter De, Dixon-Salazar, Tracy, Guerrini, Renzo, Kwan, Patrick, Marson, Anthony G., Stewart, Randy, Depondt, Chantal, Dlugos, Dennis J., Scheffer, Ingrid E., Striano, Pasquale, Freyer, Catharine, McKenna, Kevin, Regan, Brigid M., Bellows, Susannah T., Leu, Costin, Bennett, Caitlin A., Johns, Esther M. C., Macdonald, Alexandra, Shilling, Hannah, Burgess, Rosemary, Weckhuysen, Dorien, Bahlo, Melanie, O’Brien, Terence J., Todaro, Marian, Stamberger, Hannah, Andrade, Danielle M., Sadoway, Tara R., Mo, Kelly, Krestel, Heinz, Gallati, Sabina, Papacostas, Savvas S., Kousiappa, Ioanna, Tanteles, George A., Štěrbová, Katalin, Vlčková, Markéta, Sedláčková, Lucie, Laššuthová, Petra, Klein, Karl Martin, Rosenow, Felix, Reif, Philipp S., Knake, Susanne, Kunz, Wolfram S., Zsurka, Gábor, Elger, Christian E., Bauer, Jürgen, Rademacher, Michael, Pendziwiat, Manuela, Muhle, Hiltrud, Rademacher, Annika, Baalen, Andreas Van, Spiczak, Sarah Von, Stephani, Ulrich, Afawi, Zaid, Korczyn, Amos D., Kanaan, Moien, Canavati, Christina, Kurlemann, Gerhard, Müller-Schlüter, Karen, Kluger, Gerhard, Häusler, Martin, Blatt, Ilan, Lemke, Johannes R., Krey, Ilona, Weber, Yvonne G., Wolking, Stefan, Becker, Felicitas, Hengsbach, Christian, Rau, Sarah, Maisch, Ana F., Steinhoff, Bernhard J., Schulze-Bonhage, Andreas, Schubert-Bast, Susanne, Schreiber, Herbert, Borggräfe, Ingo, Schankin, Christoph J., Mayer, Thomas, Korinthenberg, Rudolf, Brockmann, Knut, Dennig, Dieter, Madeleyn, Rene, Kälviäinen, Reetta, Auvinen, Pia, Saarela, Anni, Linnankivi, Tarja, Lehesjoki, Anna-Elina, Rees, Mark I., Chung, Seo-Kyung, Pickrell, William O., Powell, Robert, Schneider, Natascha, Balestrini, Simona, Zagaglia, Sara, Braatz, Vera, Johnson, Michael R., Auce, Pauls, Sills, Graeme J., Baum, Larry W., Sham, Pak C., Cherny, Stacey S., Lui, Colin H. T., Barišić, Nina, Delanty, Norman, Doherty, Colin P., Shukralla, Arif, McCormack, Mark, El-Naggar, Hany, Canafoglia, Laura, Franceschetti, Silvana, Castellotti, Barbara, Granata, Tiziana, Zara, Federico, Iacomino, Michele, Madia, Francesca, Vari, Maria Stella, Mancardi, Maria Margherita, Salpietro, Vincenzo, Bisulli, Francesca, Tinuper, Paolo, Licchetta, Laura, Pippucci, Tommaso, Stipa, Carlotta, Minardi, Raffaella, Gambardella, Antonio, Labate, Angelo, Annesi, Grazia, Manna, Lorella, Gagliardi, Monica, Parrini, Elena, Mei, Davide, Vetro, Annalisa, Bianchini, Claudia, Montomoli, Martino, Doccini, Viola, Marini, Carla, Suzuki, Toshimitsu, Inoue, Yushi, Yamakawa, Kazuhiro, Tumiene, Birute, Sadleir, Lynette G., King, Chontelle, Mountier, Emily, Caglayan, S. Hande, Arslan, Mutluay, Yapıcı, Zuhal, Yis, Uluc, Topaloglu, Pınar, Kara, Bulent, Turkdogan, Dilsad, Gundogdu-Eken, Aslı, Bebek, Nerses, Uğur-İşeri, Sibel, Baykan, Betül, Salman, Barış, Haryanyan, Garen, Yücesan, Emrah, Kesim, Yeşim, Özkara, Çiğdem, Poduri, Annapurna, Shiedley, Beth R., Shain, Catherine, Buono, Russell J., Ferraro, Thomas N., Sperling, Michael R., Lo, Warren, Privitera, Michael, French, Jacqueline A., Schachter, Steven, Kuzniecky, Ruben I., Devinsky, Orrin, Hegde, Manu, Khankhanian, Pouya, Helbig, Katherine L., Ellis, Colin A., Spalletta, Gianfranco, Piras, Fabrizio, Piras, Federica, Gili, Tommaso, Ciullo, Valentina, Reif, Andreas, McQuillin, Andrew, Bass, Nick, McIntosh, Andrew, Blackwood, Douglas, Johnstone, Mandy, Palotie, Aarno, Pato, Michele T., Pato, Carlos N., Bromet, Evelyn J., Carvalho, Celia Barreto, Achtyes, Eric D., Azevedo, Maria Helena, Kotov, Roman, Lehrer, Douglas S., Malaspina, Dolores, Marder, Stephen R., Medeiros, Helena, Morley, Christopher P., Perkins, Diana O., Sobell, Janet L., Buckley, Peter F., Macciardi, Fabio, Rapaport, Mark H., Knowles, James A., Fanous, Ayman H., McCarroll, Steven A., Gupta, Namrata, Gabriel, Stacey B., Daly, Mark J., Lander, Eric S., Lowenstein, Daniel H., Goldstein, David B., Lerche, Holger, Berkovic, Samuel F., and Neale, Benjamin M.
Abstract: Sequencing-based studies have identified novel risk genes associated with severe epilepsies and revealed an excess of rare deleterious variation in less-severe forms of epilepsy. To identify the shared and distinct ultra-rare genetic risk factors for different types of epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals and 8,436 controls of European ancestry. We focused on three phenotypic groups: severe developmental and epileptic encephalopathies (DEEs), genetic generalized epilepsy (GGE), and non-acquired focal epilepsy (NAFE). We observed that compared to controls, individuals with any type of epilepsy carried an excess of ultra-rare, deleterious variants in constrained genes and in genes previously associated with epilepsy; we saw the strongest enrichment in individuals with DEEs and the least strong in individuals with NAFE. Moreover, we found that inhibitory GABAA receptor genes were enriched for missense variants across all three classes of epilepsy, whereas no enrichment was seen in excitatory receptor genes. The larger gene groups for the GABAergic pathway or cation channels also showed a significant mutational burden in DEEs and GGE. Although no single gene surpassed exome-wide significance among individuals with GGE or NAFE, highly constrained genes and genes encoding ion channels were among the lead associations; such genes included CACNA1G, EEF1A2, and GABRG2 for GGE and LGI1, TRIM3, and GABRG2 for NAFE. Our study, the largest epilepsy WES study to date, confirms a convergence in the genetics of severe and less-severe epilepsies associated with ultra-rare coding variation, and it highlights a ubiquitous role for GABAergic inhibition in epilepsy etiology.
Published: 2019

10. Ultra-Rare Genetic Variation in the Epilepsies: A Whole-Exome Sequencing Study of 17,606 Individuals

Author: Feng, Yen-Chen Anne, primary, Howrigan, Daniel P., additional, Abbott, Liam E., additional, Tashman, Katherine, additional, Cerrato, Felecia, additional, Singh, Tarjinder, additional, Heyne, Henrike, additional, Byrnes, Andrea, additional, Churchhouse, Claire, additional, Watts, Nick, additional, Solomonson, Matthew, additional, Lal, Dennis, additional, Heinzen, Erin L., additional, Dhindsa, Ryan S., additional, Stanley, Kate E., additional, Cavalleri, Gianpiero L., additional, Hakonarson, Hakon, additional, Helbig, Ingo, additional, Krause, Roland, additional, May, Patrick, additional, Weckhuysen, Sarah, additional, Petrovski, Slavé, additional, Kamalakaran, Sitharthan, additional, Sisodiya, Sanjay M., additional, Cossette, Patrick, additional, Cotsapas, Chris, additional, De Jonghe, Peter, additional, Dixon-Salazar, Tracy, additional, Guerrini, Renzo, additional, Kwan, Patrick, additional, Marson, Anthony G., additional, Stewart, Randy, additional, Depondt, Chantal, additional, Dlugos, Dennis J., additional, Scheffer, Ingrid E., additional, Striano, Pasquale, additional, Freyer, Catharine, additional, McKenna, Kevin, additional, Regan, Brigid M., additional, Bellows, Susannah T., additional, Leu, Costin, additional, Bennett, Caitlin A., additional, Johns, Esther M.C., additional, Macdonald, Alexandra, additional, Shilling, Hannah, additional, Burgess, Rosemary, additional, Weckhuysen, Dorien, additional, Bahlo, Melanie, additional, O’Brien, Terence J., additional, Todaro, Marian, additional, Stamberger, Hannah, additional, Andrade, Danielle M., additional, Sadoway, Tara R., additional, Mo, Kelly, additional, Krestel, Heinz, additional, Gallati, Sabina, additional, Papacostas, Savvas S., additional, Kousiappa, Ioanna, additional, Tanteles, George A., additional, Štěrbová, Katalin, additional, Vlčková, Markéta, additional, Sedláčková, Lucie, additional, Laššuthová, Petra, additional, Klein, Karl Martin, additional, Rosenow, Felix, additional, Reif, Philipp S., additional, Knake, Susanne, additional, Kunz, Wolfram S., additional, Zsurka, Gábor, additional, Elger, Christian E., additional, Bauer, Jürgen, additional, Rademacher, Michael, additional, Pendziwiat, Manuela, additional, Muhle, Hiltrud, additional, Rademacher, Annika, additional, van Baalen, Andreas, additional, von Spiczak, Sarah, additional, Stephani, Ulrich, additional, Afawi, Zaid, additional, Korczyn, Amos D., additional, Kanaan, Moien, additional, Canavati, Christina, additional, Kurlemann, Gerhard, additional, Müller-Schlüter, Karen, additional, Kluger, Gerhard, additional, Häusler, Martin, additional, Blatt, Ilan, additional, Lemke, Johannes R., additional, Krey, Ilona, additional, Weber, Yvonne G., additional, Wolking, Stefan, additional, Becker, Felicitas, additional, Hengsbach, Christian, additional, Rau, Sarah, additional, Maisch, Ana F., additional, Steinhoff, Bernhard J., additional, Schulze-Bonhage, Andreas, additional, Schubert-Bast, Susanne, additional, Schreiber, Herbert, additional, Borggräfe, Ingo, additional, Schankin, Christoph J., additional, Mayer, Thomas, additional, Korinthenberg, Rudolf, additional, Brockmann, Knut, additional, Dennig, Dieter, additional, Madeleyn, Rene, additional, Kälviäinen, Reetta, additional, Auvinen, Pia, additional, Saarela, Anni, additional, Linnankivi, Tarja, additional, Lehesjoki, Anna-Elina, additional, Rees, Mark I., additional, Chung, Seo-Kyung, additional, Pickrell, William O., additional, Powell, Robert, additional, Schneider, Natascha, additional, Balestrini, Simona, additional, Zagaglia, Sara, additional, Braatz, Vera, additional, Johnson, Michael R., additional, Auce, Pauls, additional, Sills, Graeme J., additional, Baum, Larry W., additional, Sham, Pak C., additional, Cherny, Stacey S., additional, Lui, Colin H.T., additional, Barišić, Nina, additional, Delanty, Norman, additional, Doherty, Colin P., additional, Shukralla, Arif, additional, McCormack, Mark, additional, El-Naggar, Hany, additional, Canafoglia, Laura, additional, Franceschetti, Silvana, additional, Castellotti, Barbara, additional, Granata, Tiziana, additional, Zara, Federico, additional, Iacomino, Michele, additional, Madia, Francesca, additional, Vari, Maria Stella, additional, Mancardi, Maria Margherita, additional, Salpietro, Vincenzo, additional, Bisulli, Francesca, additional, Tinuper, Paolo, additional, Licchetta, Laura, additional, Pippucci, Tommaso, additional, Stipa, Carlotta, additional, Minardi, Raffaella, additional, Gambardella, Antonio, additional, Labate, Angelo, additional, Annesi, Grazia, additional, Manna, Lorella, additional, Gagliardi, Monica, additional, Parrini, Elena, additional, Mei, Davide, additional, Vetro, Annalisa, additional, Bianchini, Claudia, additional, Montomoli, Martino, additional, Doccini, Viola, additional, Marini, Carla, additional, Suzuki, Toshimitsu, additional, Inoue, Yushi, additional, Yamakawa, Kazuhiro, additional, Tumiene, Birute, additional, Sadleir, Lynette G., additional, King, Chontelle, additional, Mountier, Emily, additional, Caglayan, S. Hande, additional, Arslan, Mutluay, additional, Yapıcı, Zuhal, additional, Yis, Uluc, additional, Topaloglu, Pınar, additional, Kara, Bulent, additional, Turkdogan, Dilsad, additional, Gundogdu-Eken, Aslı, additional, Bebek, Nerses, additional, Uğur-İşeri, Sibel, additional, Baykan, Betül, additional, Salman, Barış, additional, Haryanyan, Garen, additional, Yücesan, Emrah, additional, Kesim, Yeşim, additional, Özkara, Çiğdem, additional, Poduri, Annapurna, additional, Shiedley, Beth R., additional, Shain, Catherine, additional, Buono, Russell J., additional, Ferraro, Thomas N., additional, Sperling, Michael R., additional, Lo, Warren, additional, Privitera, Michael, additional, French, Jacqueline A., additional, Schachter, Steven, additional, Kuzniecky, Ruben I., additional, Devinsky, Orrin, additional, Hegde, Manu, additional, Khankhanian, Pouya, additional, Helbig, Katherine L., additional, Ellis, Colin A., additional, Spalletta, Gianfranco, additional, Piras, Fabrizio, additional, Piras, Federica, additional, Gili, Tommaso, additional, Ciullo, Valentina, additional, Reif, Andreas, additional, McQuillin, Andrew, additional, Bass, Nick, additional, McIntosh, Andrew, additional, Blackwood, Douglas, additional, Johnstone, Mandy, additional, Palotie, Aarno, additional, Pato, Michele T., additional, Pato, Carlos N., additional, Bromet, Evelyn J., additional, Carvalho, Celia Barreto, additional, Achtyes, Eric D., additional, Azevedo, Maria Helena, additional, Kotov, Roman, additional, Lehrer, Douglas S., additional, Malaspina, Dolores, additional, Marder, Stephen R., additional, Medeiros, Helena, additional, Morley, Christopher P., additional, Perkins, Diana O., additional, Sobell, Janet L., additional, Buckley, Peter F., additional, Macciardi, Fabio, additional, Rapaport, Mark H., additional, Knowles, James A., additional, Fanous, Ayman H., additional, McCarroll, Steven A., additional, Gupta, Namrata, additional, Gabriel, Stacey B., additional, Daly, Mark J., additional, Lander, Eric S., additional, Lowenstein, Daniel H., additional, Goldstein, David B., additional, Lerche, Holger, additional, Berkovic, Samuel F., additional, and Neale, Benjamin M., additional
Published: 2019
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11. Distinct gene-set burden patterns underlie common generalized and focal epilepsies

Author: Mahmoud Koko, Roland Krause, Thomas Sander, Dheeraj Reddy Bobbili, Michael Nothnagel, Patrick May, Holger Lerche, Yen-Chen Anne Feng, Daniel P Howrigan, Liam E Abbott, Katherine Tashman, Felecia Cerrato, Tarjinder Singh, Henrike Heyne, Andrea Byrnes, Claire Churchhouse, Nick Watts, Matthew Solomonson, Dennis Lal, Erin L Heinzen, Ryan S Dhindsa, Kate E Stanley, Gianpiero L Cavalleri, Hakon Hakonarson, Ingo Helbig, Sarah Weckhuysen, Slavé Petrovski, Sitharthan Kamalakaran, Sanjay M Sisodiya, Patrick Cossette, Chris Cotsapas, Peter DeJonghe, Tracy Dixon-Salazar, Renzo Guerrini, Patrick Kwan, Anthony G Marson, Randy Stewart, Chantal Depondt, Dennis J Dlugos, Ingrid E Scheffer, Pasquale Striano, Catharine Freyer, Kevin McKenna, Brigid M Regan, Susannah T Bellows, Costin Leu, Caitlin A Bennett, Esther M C Johns, Alexandra Macdonald, Hannah Shilling, Rosemary Burgess, Dorien Weckhuysen, Melanie Bahlo, Terence J O'Brien, Marian Todaro, Hannah Stamberger, Danielle M Andrade, Tara R Sadoway, Kelly Mo, Heinz Krestel, Sabina Gallati, Savvas S Papacostas, Ioanna Kousiappa, George A Tanteles, Katalin Štěrbová, Markéta Vlčková, Lucie Sedláčková, Petra Laššuthová, Karl Martin Klein, Felix Rosenow, Philipp S Reif, Susanne Knake, Wolfram S Kunz, Gábor Zsurka, Christian E Elger, Jürgen Bauer, Michael Rademacher, Manuela Pendziwiat, Hiltrud Muhle, Annika Rademacher, Andreas vanBaalen, Sarah vonSpiczak, Ulrich Stephani, Zaid Afawi, Amos D Korczyn, Moien Kanaan, Christina Canavati, Gerhard Kurlemann, Karen Müller-Schlüter, Gerhard Kluger, Martin Häusler, Ilan Blatt, Johannes R Lemke, Ilona Krey, Yvonne G Weber, Stefan Wolking, Felicitas Becker, Christian Hengsbach, Sarah Rau, Ana F Maisch, Bernhard J Steinhoff, Andreas Schulze-Bonhage, Susanne Schubert-Bast, Herbert Schreiber, Ingo Borggräfe, Christoph J Schankin, Thomas Mayer, Rudolf Korinthenberg, Knut Brockmann, Dieter Dennig, Rene Madeleyn, Reetta Kälviäinen, Pia Auvinen, Anni Saarela, Tarja Linnankivi, Anna-Elina Lehesjoki, Mark I Rees, Seo-Kyung Chung, William O Pickrell, Robert Powell, Natascha Schneider, Simona Balestrini, Sara Zagaglia, Vera Braatz, Michael R Johnson, Pauls Auce, Graeme J Sills, Larry W Baum, Pak C Sham, Stacey S Cherny, Colin H T Lui, Nina Barišić, Norman Delanty, Colin P Doherty, Arif Shukralla, Mark McCormack, Hany El-Naggar, Laura Canafoglia, Silvana Franceschetti, Barbara Castellotti, Tiziana Granata, Federico Zara, Michele Iacomino, Francesca Madia, Maria Stella Vari, Maria Margherita Mancardi, Vincenzo Salpietro, Francesca Bisulli, Paolo Tinuper, Laura Licchetta, Tommaso Pippucci, Carlotta Stipa, Raffaella Minardi, Antonio Gambardella, Angelo Labate, Grazia Annesi, Lorella Manna, Monica Gagliardi, Elena Parrini, Davide Mei, Annalisa Vetro, Claudia Bianchini, Martino Montomoli, Viola Doccini, Carla Marini, Toshimitsu Suzuki, Yushi Inoue, Kazuhiro Yamakawa, Birute Tumiene, Lynette G Sadleir, Chontelle King, Emily Mountier, Hande S Caglayan, Mutluay Arslan, Zuhal Yapıcı, Uluc Yis, Pınar Topaloglu, Bulent Kara, Dilsad Turkdogan, Aslı Gundogdu-Eken, Nerses Bebek, Sibel Uğur-İşeri, Betül Baykan, Barış Salman, Garen Haryanyan, Emrah Yücesan, Yeşim Kesim, Çiğdem Özkara, Annapurna Poduri, Beth R Shiedley, Catherine Shain, Russell J Buono, Thomas N Ferraro, Michael R Sperling, Warren Lo, Michael Privitera, Jacqueline A French, Steven Schachter, Ruben I Kuzniecky, Orrin Devinsky, Manu Hegde, Pouya Khankhanian, Katherine L Helbig, Colin A Ellis, Gianfranco Spalletta, Fabrizio Piras, Federica Piras, Tommaso Gili, Valentina Ciullo, Andreas Reif, Andrew McQuillin, Nick Bass, Andrew McIntosh, Douglas Blackwood, Mandy Johnstone, Aarno Palotie, Michele T Pato, Carlos N Pato, Evelyn J Bromet, Celia Barreto Carvalho, Eric D Achtyes, Maria Helena Azevedo, Roman Kotov, Douglas S Lehrer, Dolores Malaspina, Stephen R Marder, Helena Medeiros, Christopher P Morley, Diana O Perkins, Janet L Sobell, Peter F Buckley, Fabio Macciardi, Mark H Rapaport, James A Knowles, Genomic Psychiatry Cohort, Ayman H Fanous, Steven A McCarroll, Namrata Gupta, Stacey B Gabriel, Mark J Daly, Eric S Lander, Daniel H Lowenstein, David B Goldstein, Samuel F Berkovic, Benjamin M Neale, Epi25 Collaborative, Koko M., Krause R., Sander T., Bobbili D.R., Nothnagel M., May P., Lerche H., Bisulli F., Tinuper P., Pippucci T., Abbott, Liam E., Hengsbach, Christian, Rau, Sarah, Maisch, Ana F., Steinhoff, Bernhard J., Schulze-Bonhage, Andreas, Schubert-Bast, Susanne, Schreiber, Herbert, Borggräfe, Ingo, Schankin, Christoph J., Mayer, Thomas, Tashman, Katherine, Korinthenberg, Rudolf, Brockmann, Knut, Kurlemann, Gerhard, Dennig, Dieter, Madeleyn, Rene, Kälviäinen, Reetta, Auvinen, Pia, Saarela, Anni, Linnankivi, Tarja, Lehesjoki, Anna-Elina, Cerrato, Felecia, Rees, Mark I., Chung, Seo-Kyung, Pickrell, William O., Powell, Robert, Schneider, Natascha, Balestrini, Simona, Zagaglia, Sara, Braatz, Vera, Johnson, Michael R., Auce, Pauls, Singh, Tarjinder, Sills, Graeme J., Baum, Larry W., Sham, Pak C., Cherny, Stacey S., Lui, Colin H. T., Barišic, Nina, Delanty, Norman, Doherty, Colin P., Shukralla, Arif, McCormack, Mark, Heyne, Henrike, El-Naggar, Hany, Canafoglia, Laura, Franceschetti, Silvana, Castellotti, Barbara, Granata, Tiziana, Zara, Federico, Iacomino, Michele, Madia, Francesca, Vari, Maria Stella, Mancardi, Maria Margherita, Byrnes, Andrea, Salpietro, Vincenzo, Bisulli, Francesca, Tinuper, Paolo, Licchetta, Laura, Pippucci, Tommaso, Stipa, Carlotta, Minardi, Raffaella, Gambardella, Antonio, Labate, Angelo, Annesi, Grazia, Churchhouse, Claire, Manna, Lorella, Gagliardi, Monica, Parrini, Elena, Mei, Davide, Vetro, Annalisa, Bianchini, Claudia, Montomoli, Martino, Doccini, Viola, Marini, Carla, Suzuki, Toshimitsu, Watts, Nick, Inoue, Yushi, Yamakawa, Kazuhiro, Tumiene, Birute, Sadleir, Lynette G., King, Chontelle, Mountier, Emily, Caglayan, Hande S., Arslan, Mutluay, Yapici, Zuhal, Yis, Uluc, Solomonson, Matthew, Topaloglu, Pinar, Kara, Bulent, Turkdogan, Dilsad, Gundogdu-Eken, Asli, Bebek, Nerses, Ugur-Iseri, Sibel, Baykan, Betül, Salman, Baris, Haryanyan, Garen, Yücesan, Emrah, Lal, Dennis, Kesim, Yesim, Özkara, Çigdem, Poduri, Annapurna, Shiedley, Beth R., Shain, Catherine, Buono, Russell J., Ferraro, Thomas N., Sperling, Michael R., Lo, Warren, Privitera, Michael, Heinzen, Erin L., French, Jacqueline A., Schachter, Steven, Kuzniecky, Ruben I., Devinsky, Orrin, Hegde, Manu, Khankhanian, Pouya, Helbig, Katherine L., Ellis, Colin A., Spalletta, Gianfranco, Piras, Fabrizio, Dhindsa, Ryan S., Piras, Federica, Gili, Tommaso, Ciullo, Valentina, Reif, Andreas, McQuillin, Andrew, Bass, Nick, McIntosh, Andrew, Blackwood, Douglas, Johnstone, Mandy, Palotie, Aarno, Stanley, Kate E., Pato, Michele T., Pato, Carlos N., Bromet, Evelyn J., Carvalho, Celia Barreto, Achtyes, Eric D., Azevedo, Maria Helena, Kotov, Roman, Lehrer, Douglas S., Malaspina, Dolores, Marder, Stephen R., Cavalleri, Gianpiero L., Medeiros, Helena, Morley, Christopher P., Perkins, Diana O., Sobell, Janet L., Buckley, Peter F., Macciardi, Fabio, Rapaport, Mark H., Knowles, James A., Cohort, Genomic Psychiatry, Fanous, Ayman H., Hakonarson, Hakon, McCarroll, Steven A., Gupta, Namrata, Gabriel, Stacey B., Daly, Mark J., Lander, Eric S., Lowenstein, Daniel H., Goldstein, David B., Lerche, Holger, Berkovic, Samuel F., Neale, Benjamin M., Helbig, Ingo, Krause, Roland, May, Patrick, Weckhuysen, Sarah, Petrovski, Slavé, Kamalakaran, Sitharthan, Sisodiya, Sanjay M., Cossette, Patrick, Cotsapas, Chris, DeJonghe, Peter, Dixon-Salazar, Tracy, Guerrini, Renzo, Kwan, Patrick, Marson, Anthony G., Stewart, Randy, Depondt, Chantal, Dlugos, Dennis J., Scheffer, Ingrid E., Striano, Pasquale, Freyer, Catharine, McKenna, Kevin, Regan, Brigid M., Bellows, Susannah T., Leu, Costin, Bennett, Caitlin A., Johns, Esther M. C., Macdonald, Alexandra, Shilling, Hannah, Burgess, Rosemary, Weckhuysen, Dorien, Bahlo, Melanie, O'Brien, Terence J., Todaro, Marian, Stamberger, Hannah, Andrade, Danielle M., Sadoway, Tara R., Mo, Kelly, Krestel, Heinz, Gallati, Sabina, Papacostas, Savvas S., Kousiappa, Ioanna, Tanteles, George A., Šterbová, Katalin, Vlcková, Markéta, Sedlácková, Lucie, Laššuthová, Petra, Klein, Karl Martin, Rosenow, Felix, Reif, Philipp S., Knake, Susanne, Kunz, Wolfram S., Zsurka, Gábor, Elger, Christian E., Bauer, Jürgen, Rademacher, Michael, Feng, Yen-Chen Anne, Pendziwiat, Manuela, Muhle, Hiltrud, Rademacher, Annika, van Baalen, Andreas, von Spiczak, Sarah, Stephani, Ulrich, Afawi, Zaid, Korczyn, Amos D., Kanaan, Moien, Canavati, Christina, Howrigan, Daniel P., Müller-Schlüter, Karen, Kluger, Gerhard, Häusler, Martin, Blatt, Ilan, Lemke, Johannes R., Krey, Ilona, Weber, Yvonne G., Wolking, Stefan, Becker, Felicitas, DFG Research Unit FOR-2715 (Germany), FNR (Luxembourg), NHGRI (US), NHLBI (US), DAAD (Germany). [sponsor], and Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center]
Subjects: Exome sequencing, Male, Medicine (General), Neurology [D14] [Human health sciences], Gene-set, Genome-wide association study, Disease, Biology, Epileptogenesis, General Biochemistry, Genetics and Molecular Biology, Whole Exome Sequencing, Epilepsy, R5-920, medicine, Missense mutation, Humans, Exome, Genetic Predisposition to Disease, Gene, Genetic association, Ultra-rare variant, Genetics, Neurologie [D14] [Sciences de la santé humaine], Burden analysis, Genetic Variation, General Medicine, medicine.disease, Ultra-rare variants, Gene-sets, Case-Control Studies, Medicine, epilepsy, Epilepsy, Generalized, Female, Genetics & genetic processes [F10] [Life sciences], Epilepsies, Partial, Human medicine, Burden analysi, Génétique & processus génétiques [F10] [Sciences du vivant], Case-Control Studie, Research Paper, Genome-Wide Association Study, Human
Abstract: EBioMedicine 72, 103588 (2021). doi:10.1016/j.ebiom.2021.103588, Published by Elsevier, Amsterdam [u.a.]
Published: 2021
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12. Epilepsy care pathway: The Finnish model.

Author: Kälviäinen R, Hadj-Allal Z, Kirjavainen J, Roivainen R, Linnankivi T, Peltola J, Eriksson K, Lamusuo S, Lähdesmäki T, Annunen J, Vieira P, Tarkiainen V, Jutila L, Saarela A, Kämppi L, Metsähonkala L, Gaily E, Lähde N, Antinmaa J, Erme S, Pirttisalo AL, Virolainen J, Ylijoki M, Kela L, Komulainen-Ebrahim J, and Sorjonen P
Abstract: Objective: Integrated care pathways are essential for consistent, effective epilepsy care, offering equal access and quality regardless of socioeconomic status. They must align with the WHO Global Action Plan on Epilepsy, ensuring best practices and cost-effective management. We describe the Finnish national epilepsy care pathway, which includes multiple levels of care, from initial diagnosis to long-term care for all types of epilepsy, with a specific focus on rare and complex cases integrated with the European Reference Network (ERN) for Rare and Complex Epilepsies EpiCARE., Methods: In 2017, the Finnish government nominated Kuopio University Hospital to coordinate diagnostics and care for severe epilepsy in Finland. A national multidisciplinary consensus panel, including specialists from both adult and pediatric neurology departments across all five Finnish university hospitals and from the patient organization, was established. The resulting pathway was adopted into the current Finnish evidence-based current care guidelines for epilepsy., Results: The Finnish epilepsy care pathway focuses on timely referrals, continuity of care and enhanced communication between healthcare providers at different levels of care. Patient involvement is assured with an individualized digital application offering secure online messaging, a seizure calendar, and remote visits. The pathway enhances virtual consultations and includes regular national diagnostic multidisciplinary meetings for severe epilepsies before selected cases are consulted in ERN EpiCARE meetings., Significance: This Finnish model for epilepsy care provides a streamlined, multidisciplinary approach to diagnosis and treatment and combines modern digital tools, data sharing, and peer support. This pathway can serve to model how integrated healthcare systems can effectively manage complex conditions., Plain Language Summary: We describe the Finnish national epilepsy care pathway, which includes multiple levels of care, from initial diagnosis to long-term care for all types of epilepsy, with a specific focus on rare and complex cases integrated with the European Reference Network (ERN) for Rare and Complex Epilepsies EpiCARE. Finnish model for epilepsy care provides a streamlined, multidisciplinary approach to diagnosis and long-term treatment of epilepsy. The pathway enhances virtual consultations and includes national and European-level diagnostic multidisciplinary meetings for severe epilepsies. To improve outcomes, we emphasize the use of modern digital tools, data sharing, and peer support., (© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
Published: 2024
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13. Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Author: Chen S, Abou-Khalil BW, Afawi Z, Ali QZ, Amadori E, Anderson A, Anderson J, Andrade DM, Annesi G, Arslan M, Auce P, Bahlo M, Baker MD, Balagura G, Balestrini S, Banks E, Barba C, Barboza K, Bartolomei F, Bass N, Baum LW, Baumgartner TH, Baykan B, Bebek N, Becker F, Bennett CA, Beydoun A, Bianchini C, Bisulli F, Blackwood D, Blatt I, Borggräfe I, Bosselmann C, Braatz V, Brand H, Brockmann K, Buono RJ, Busch RM, Caglayan SH, Canafoglia L, Canavati C, Castellotti B, Cavalleri GL, Cerrato F, Chassoux F, Cherian C, Cherny SS, Cheung CL, Chou IJ, Chung SK, Churchhouse C, Ciullo V, Clark PO, Cole AJ, Cosico M, Cossette P, Cotsapas C, Cusick C, Daly MJ, Davis LK, Jonghe P, Delanty N, Dennig D, Depondt C, Derambure P, Devinsky O, Di Vito L, Dickerson F, Dlugos DJ, Doccini V, Doherty CP, El-Naggar H, Ellis CA, Epstein L, Evans M, Faucon A, Feng YA, Ferguson L, Ferraro TN, Da Silva IF, Ferri L, Feucht M, Fields MC, Fitzgerald M, Fonferko-Shadrach B, Fortunato F, Franceschetti S, French JA, Freri E, Fu JM, Gabriel S, Gagliardi M, Gambardella A, Gauthier L, Giangregorio T, Gili T, Glauser TA, Goldberg E, Goldman A, Goldstein DB, Granata T, Grant R, Greenberg DA, Guerrini R, Gundogdu-Eken A, Gupta N, Haas K, Hakonarson H, Haryanyan G, Häusler M, Hegde M, Heinzen EL, Helbig I, Hengsbach C, Heyne H, Hirose S, Hirsch E, Ho CJ, Hoeper O, Howrigan DP, Hucks D, Hung PC, Iacomino M, Inoue Y, Inuzuka LM, Ishii A, Jehi L, Johnson MR, Johnstone M, Kälviäinen R, Kanaan M, Kara B, Kariuki SM, Kegele J, Kesim Y, Khoueiry-Zgheib N, Khoury J, King C, Klein KM, Kluger G, Knake S, Kok F, Korczyn AD, Korinthenberg R, Koupparis A, Kousiappa I, Krause R, Krenn M, Krestel H, Krey I, Kunz WS, Kurlemann G, Kuzniecky RI, Kwan P, La Vega-Talbott M, Labate A, Lacey A, Lal D, Laššuthová P, Lauxmann S, Lawthom C, Leech SL, Lehesjoki AE, Lemke JR, Lerche H, Lesca G, Leu C, Lewin N, Lewis-Smith D, Li GH, Liao C, Licchetta L, Lin CH, Lin KL, Linnankivi T, Lo W, Lowenstein DH, Lowther C, Lubbers L, Lui CHT, Macedo-Souza LI, Madeleyn R, Madia F, Magri S, Maillard L, Marcuse L, Marques P, Marson AG, Matthews AG, May P, Mayer T, McArdle W, McCarroll SM, McGoldrick P, McGraw CM, McIntosh A, McQuillan A, Meador KJ, Mei D, Michel V, Millichap JJ, Minardi R, Montomoli M, Mostacci B, Muccioli L, Muhle H, Müller-Schlüter K, Najm IM, Nasreddine W, Neaves S, Neubauer BA, Newton CRJC, Noebels JL, Northstone K, Novod S, O'Brien TJ, Owusu-Agyei S, Özkara Ç, Palotie A, Papacostas SS, Parrini E, Pato C, Pato M, Pendziwiat M, Pennell PB, Petrovski S, Pickrell WO, Pinsky R, Pinto D, Pippucci T, Piras F, Piras F, Poduri A, Pondrelli F, Posthuma D, Powell RHW, Privitera M, Rademacher A, Ragona F, Ramirez-Hamouz B, Rau S, Raynes HR, Rees MI, Regan BM, Reif A, Reinthaler E, Rheims S, Ring SM, Riva A, Rojas E, Rosenow F, Ryvlin P, Saarela A, Sadleir LG, Salman B, Salmon A, Salpietro V, Sammarra I, Scala M, Schachter S, Schaller A, Schankin CJ, Scheffer IE, Schneider N, Schubert-Bast S, Schulze-Bonhage A, Scudieri P, Sedláčková L, Shain C, Sham PC, Shiedley BR, Siena SA, Sills GJ, Sisodiya SM, Smoller JW, Solomonson M, Spalletta G, Sparks KR, Sperling MR, Stamberger H, Steinhoff BJ, Stephani U, Štěrbová K, Stewart WC, Stipa C, Striano P, Strzelczyk A, Surges R, Suzuki T, Talarico M, Talkowski ME, Taneja RS, Tanteles GA, Timonen O, Timpson NJ, Tinuper P, Todaro M, Topaloglu P, Tsai MH, Tumiene B, Turkdogan D, Uğur-İşeri S, Utkus A, Vaidiswaran P, Valton L, van Baalen A, Vari MS, Vetro A, Vlčková M, von Brauchitsch S, von Spiczak S, Wagner RG, Watts N, Weber YG, Weckhuysen S, Widdess-Walsh P, Wiebe S, Wolf SM, Wolff M, Wolking S, Wong I, von Wrede R, Wu D, Yamakawa K, Yapıcı Z, Yis U, Yolken R, Yücesan E, Zagaglia S, Zahnert F, Zara F, Zimprich F, Zizovic M, Zsurka G, Neale BM, and Berkovic SF
Abstract: Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance. Genes encoding ion channels show strong association with multiple epilepsy subtypes, including epileptic encephalopathies, generalized and focal epilepsies, while most other gene discoveries are subtype-specific, highlighting distinct genetic contributions to different epilepsies. Combining results from rare single nucleotide/short indel-, copy number-, and common variants, we offer an expanded view of the genetic architecture of epilepsy, with growing evidence of convergence among different genetic risk loci on the same genes. Top candidate genes are enriched for roles in synaptic transmission and neuronal excitability, particularly postnatally and in the neocortex. We also identify shared rare variant risk between epilepsy and other neurodevelopmental disorders. Our data can be accessed via an interactive browser, hopefully facilitating diagnostic efforts and accelerating the development of follow-up studies., Competing Interests: Competing Interests B.M.N is a member of the scientific advisory board at Deep Genomics and Neumora. No other authors have competing interests to declare
Published: 2024
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14. Novel LAMC3 pathogenic variant enriched in Finnish population causes malformations of cortical development and severe epilepsy.

Author: Saarela A, Timonen O, Kirjavainen J, Liu Y, Silvennoinen K, Mervaala E, and Kälviäinen R
Subjects: Humans, Finland, Female, Male, Child, Child, Preschool, Phenotype, Adolescent, Mutation, Malformations of Cortical Development genetics, Malformations of Cortical Development physiopathology, Malformations of Cortical Development complications, Epilepsy genetics, Epilepsy physiopathology, Epilepsy etiology, Laminin genetics
Abstract: Objective: Recessive LAMC3 mutations are recognized to cause epilepsy with cortical malformations characterized by polymicrogyria and pachygyria. The objective of this study was to describe the clinical picture and epilepsy phenotype of four patients with a previously undescribed LAMC3 variant., Methods: All epilepsy patients treated in Kuopio Epilepsy Center (located in Kuopio, Finland) are offered the possibility to participate in a scientific study investigating biomarkers in epilepsy (Epibiomarker study). We have collected a comprehensive database of the study population, and are currently re-evaluating our database regarding the patients with developmental and/or epileptic encephalopathy (DEE). If the etiology of epilepsy remains unknown in the clinical setting, we are performing whole exome sequencing to recognize the genetic causes., Results: Among our study population of 323 DEE patients we recognized three patients with similar homozygous LAMC3 c.1866del (p.(Phe623Serfs*10)) frameshift variant and one patient with a compound heterozygous mutation where the same frameshift variant was combined with an intronic LAMC3 c.4231-12C>G variant on another allele. All these patients have severe epilepsy and either bilateral agyria-pachygyria or bilateral polymicrogyria in their clinical MRI scanning. Cortical malformations involve the occipital lobes in all our patients. Epilepsy phenotype is variable as two of our patients have DEE with epileptic spasms progressing to Lennox-Gastaut syndrome and intellectual disability. The other two patients have focal epilepsy without marked cognitive deficit. The four patients are unrelated. LAMC3 c.1866del p.(Phe623Serfs*10) frameshift variant is enriched in the Finnish population., Significance: Only a few patients with epilepsy caused by LAMC3 homozygous or compound heterozygous mutations have been described in the literature. To our knowledge, the variants discovered in our patients have not previously been published. Clinical phenotype appears to be more varied than previously assumed and patients with a milder phenotype and normal cognition have probably remained unrecognized., (© 2024 The Author(s). Epileptic Disorders published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
Published: 2024
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14 results on '"Saarela, Anni"'

1. Exome sequencing reveals predominantly de novo variants in disorders with intellectual disability (ID) in the founder population of Finland

2. Seizure outcome and use of antiepileptic drugs after epilepsy surgery according to histopathological diagnosis: a retrospective multicentre cohort study

3. Novel LAMC3pathogenic variant enriched in Finnish population causes malformations of cortical development and severe epilepsy

4. Sub-genic intolerance, ClinVar, and the epilepsies: A whole-exome sequencing study of 29,165 individuals

5. Distinct gene-set burden patterns underlie common generalized and focal epilepsies

6. Sub-genic intolerance, ClinVar, and the epilepsies: A whole-exome sequencing study of 29,165 individuals

7. Epilepsy Subtype-Specific Copy Number Burden Observed in a Genome-Wide Study of 17 458 Subjects

8. Seizure outcome and use of antiepileptic drugs after epilepsy surgery according to histopathological diagnosis: a retrospective multicentre cohort study

9. Ultra-Rare Genetic Variation in the Epilepsies: A Whole-Exome Sequencing Study of 17,606 Individuals

10. Ultra-Rare Genetic Variation in the Epilepsies: A Whole-Exome Sequencing Study of 17,606 Individuals

11. Distinct gene-set burden patterns underlie common generalized and focal epilepsies

12. Epilepsy care pathway: The Finnish model.

13. Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

14. Novel LAMC3 pathogenic variant enriched in Finnish population causes malformations of cortical development and severe epilepsy.

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