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Your search keyword '"Yevgeniya Abramzon"' showing total 10 results
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10 results on '"Yevgeniya Abramzon"'

1. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

Author

Aude Nicolas, Kevin P. Kenna, Alan E. Renton, Nicola Ticozzi, Faraz Faghri, Ruth Chia, Janice A. Dominov, Brendan J. Kenna, Mike A. Nalls, Pamela Keagle, Alberto M. Rivera, Wouter van Rheenen, Natalie A. Murphy, Joke J.F.A. van Vugt, Joshua T. Geiger, Rick A. Van der Spek, Hannah A. Pliner, null Shankaracharya, Bradley N. Smith, Giuseppe Marangi, Simon D. Topp, Yevgeniya Abramzon, Athina Soragia Gkazi, John D. Eicher, Aoife Kenna, Gabriele Mora, Andrea Calvo, Letizia Mazzini, Nilo Riva, Jessica Mandrioli, Claudia Caponnetto, Stefania Battistini, Paolo Volanti, Vincenzo La Bella, Francesca L. Conforti, Giuseppe Borghero, Sonia Messina, Isabella L. Simone, Francesca Trojsi, Fabrizio Salvi, Francesco O. Logullo, Sandra D’Alfonso, Lucia Corrado, Margherita Capasso, Luigi Ferrucci, Cristiane de Araujo Martins Moreno, Sitharthan Kamalakaran, David B. Goldstein, Aaron D. Gitler, Tim Harris, Richard M. Myers, Hemali Phatnani, Rajeeva Lochan Musunuri, Uday Shankar Evani, Avinash Abhyankar, Michael C. Zody, Julia Kaye, Steven Finkbeiner, Stacia K. Wyman, Alex LeNail, Leandro Lima, Ernest Fraenkel, Clive N. Svendsen, Leslie M. Thompson, Jennifer E. Van Eyk, James D. Berry, Timothy M. Miller, Stephen J. Kolb, Merit Cudkowicz, Emily Baxi, Michael Benatar, J. Paul Taylor, Evadnie Rampersaud, Gang Wu, Joanne Wuu, Giuseppe Lauria, Federico Verde, Isabella Fogh, Cinzia Tiloca, Giacomo P. Comi, Gianni Sorarù, Cristina Cereda, Philippe Corcia, Hannu Laaksovirta, Liisa Myllykangas, Lilja Jansson, Miko Valori, John Ealing, Hisham Hamdalla, Sara Rollinson, Stuart Pickering-Brown, Richard W. Orrell, Katie C. Sidle, Andrea Malaspina, John Hardy, Andrew B. Singleton, Janel O. Johnson, Sampath Arepalli, Peter C. Sapp, Diane McKenna-Yasek, Meraida Polak, Seneshaw Asress, Safa Al-Sarraj, Andrew King, Claire Troakes, Caroline Vance, Jacqueline de Belleroche, Frank Baas, Anneloor L.M.A. ten Asbroek, José Luis Muñoz-Blanco, Dena G. Hernandez, Jinhui Ding, J. Raphael Gibbs, Sonja W. Scholz, Mary Kay Floeter, Roy H. Campbell, Francesco Landi, Robert Bowser, Stefan M. Pulst, John M. Ravits, Daniel J.L. MacGowan, Janine Kirby, Erik P. Pioro, Roger Pamphlett, James Broach, Glenn Gerhard, Travis L. Dunckley, Christopher B. Brady, Neil W. Kowall, Juan C. Troncoso, Isabelle Le Ber, Kevin Mouzat, Serge Lumbroso, Terry D. Heiman-Patterson, Freya Kamel, Ludo Van Den Bosch, Robert H. Baloh, Tim M. Strom, Thomas Meitinger, Aleksey Shatunov, Kristel R. Van Eijk, Mamede de Carvalho, Maarten Kooyman, Bas Middelkoop, Matthieu Moisse, Russell L. McLaughlin, Michael A. Van Es, Markus Weber, Kevin B. Boylan, Marka Van Blitterswijk, Rosa Rademakers, Karen E. Morrison, A. Nazli Basak, Jesús S. Mora, Vivian E. Drory, Pamela J. Shaw, Martin R. Turner, Kevin Talbot, Orla Hardiman, Kelly L. Williams, Jennifer A. Fifita, Garth A. Nicholson, Ian P. Blair, Guy A. Rouleau, Jesús Esteban-Pérez, Alberto García-Redondo, Ammar Al-Chalabi, Ekaterina Rogaeva, Lorne Zinman, Lyle W. Ostrow, Nicholas J. Maragakis, Jeffrey D. Rothstein, Zachary Simmons, Johnathan Cooper-Knock, Alexis Brice, Stephen A. Goutman, Eva L. Feldman, Summer B. Gibson, Franco Taroni, Antonia Ratti, Cinzia Gellera, Philip Van Damme, Wim Robberecht, Pietro Fratta, Mario Sabatelli, Christian Lunetta, Albert C. Ludolph, Peter M. Andersen, Jochen H. Weishaupt, William Camu, John Q. Trojanowski, Vivianna M. Van Deerlin, Robert H. Brown, Leonard H. van den Berg, Jan H. Veldink, Matthew B. Harms, Jonathan D. Glass, David J. Stone, Pentti Tienari, Vincenzo Silani, Adriano Chiò, Christopher E. Shaw, Bryan J. Traynor, John E. Landers, Isabella Simone, Giancarlo Logroscino, Ilaria Bartolomei, Maria Rita Murru, Emanuela Costantino, Carla Pani, Roberta Puddu, Carla Caredda, Valeria Piras, Stefania Tranquilli, Stefania Cuccu, Daniela Corongiu, Maurizio Melis, Antonio Milia, Francesco Marrosu, Maria Giovanna Marrosu, Gianluca Floris, Antonino Cannas, Gianluigi Mancardi, Paola Origone, Paola Mandich, Sebastiano Cavallaro, Kalliopi Marinou, Riccardo Sideri, Silvana Penco, Lorena Mosca, Giuseppe Lauria Pinter, Massimo Corbo, Paola Carrera, Nicola Fini, Antonio Fasano, Lucio Tremolizzo, Alessandro Arosio, Carlo Ferrarese, Gioacchino Tedeschi, Maria Rosaria Monsurrò, Giovanni Piccirillo, Cinzia Femiano, Anna Ticca, Enzo Ortu, Rossella Spataro, Tiziana Colletti, Marcella Zollino, Amelia Conte, Marco Luigetti, Serena Lattante, Marialuisa Santarelli, Antonio Petrucci, Maura Pugliatti, Angelo Pirisi, Leslie D. Parish, Patrizia Occhineri, Fabio Giannini, Claudia Ricci, Michele Benigni, Tea B. Cau, Daniela Loi, Cristina Moglia, Maura Brunetti, Marco Barberis, Gabriella Restagno, Federico Casale, Giuseppe Marrali, Giuseppe Fuda, Irene Ossola, Stefania Cammarosano, Antonio Canosa, Antonio Ilardi, Umberto Manera, Maurizio Grassano, Raffaella Tanel, Fabrizio Pisano, Neil A. Shneider, Stephen Goutman, Siddharthan Chandran, Suvankar Pal, George Manousakis, Stanley H. Appel, Ericka Simpson, Leo Wang, Summer Gibson, Richard Bedlack, David Lacomis, Dhruv Sareen, Alexander Sherman, Lucie Bruijn, Michelle Penny, Andrew S. Allen, Stanley Appel, Richard S. Bedlack, Braden E. Boone, Robert Brown, John P. Carulli, Alessandra Chesi, Wendy K. Chung, Elizabeth T. Cirulli, Gregory M. Cooper, Julien Couthouis, Aaron G. Day-Williams, Patrick A. Dion, Yujun Han, Sebastian D. Hayes, Angela L. Jones, Jonathan Keebler, Brian J. Krueger, Brittany N. Lasseigne, Shawn E. Levy, Yi-Fan Lu, Tom Maniatis, Slavé Petrovski, Alya R. Raphael, Zhong Ren, Katherine B. Sims, John F. Staropoli, Lindsay L. Waite, Quanli Wang, Jack R. Wimbish, Winnie W. Xin, Justin Kwan, James R. Broach, Ximena Arcila-Londono, Edward B. Lee, Noah Zaitlen, Gregory A. Cox, Steve Finkbeiner, Efthimios Dardiotis, Eran Hornstein, Daniel J. MacGowan, Terry Heiman-Patterson, Molly G. Hammell, Nikolaos A. Patsopoulos, Joshua Dubnau, Avindra Nath, Stacia Wyman, Alexander LeNail, Jenny Van Eyk, Stephan Züchner, Rebecca Schule, Jacob McCauley, Sumaira Hussain, Anne Cooley, Marielle Wallace, Christine Clayman, Richard Barohn, Jeffrey Statland, John Ravits, Andrea Swenson, Carlayne Jackson, Jaya Trivedi, Shaida Khan, Jonathan Katz, Liberty Jenkins, Ted Burns, Kelly Gwathmey, James Caress, Corey McMillan, Lauren Elman, Erik Pioro, Jeannine Heckmann, Yuen So, David Walk, Samuel Maiser, Jinghui Zhang, Fabiola De Marchi, Stefania Corti, Mauro Ceroni, Gabriele Siciliano, Massimiliano Filosto, Maurizio Inghilleri, Silvia Peverelli, Claudia Colombrita, Barbara Poletti, Luca Maderna, Roberto Del Bo, Stella Gagliardi, Giorgia Querin, Cinzia Bertolin, Viviana Pensato, Barbara Castellotti, Vincent Meininger, Gérard Besson, Emmeline Lagrange, Pierre Clavelou, Nathalie Guy, Philippe Couratier, Patrick Vourch, Véronique Danel, Emilien Bernard, Gwendal Lemasson, Ahmad Al Kheifat, Peter Andersen, Adriano Chio, Jonathan Cooper-Knock, Annelot Dekker, Vivian Drory, Alberto Garcia Redondo, Marc Gotkine, Winston Hide, Alfredo Iacoangeli, Jonathan Glass, Kevin Kenna, Matthew Kiernan, John Landers, Russell McLaughlin, Jonathan Mill, Miguel Mitne Neto, Mattieu Moisse, Jesus Mora Pardina, Karen Morrison, Stephen Newhouse, Susana Pinto, Sara Pulit, Pamela Shaw, Chris Shaw, William Sproviero, Gijs Tazelaar, Philip van Damme, Leonard van den Berg, Rick van der Spek, Kristel van Eijk, Michael van Es, Joke van Vugt, Jan Veldink, Mayana Zatz, Denis C. Bauer, Natalie A. Twine, Department of Neurosciences, Pentti Tienari / Principal Investigator, Neurologian yksikkö, Research Programs Unit, Clinicum, Research Programme for Molecular Neurology, University of Helsinki, Medicum, Department of Pathology, HUS Neurocenter, Nicolas A., Kenna K.P., Renton A.E., Ticozzi N., Faghri F., Chia R., Dominov J.A., Kenna B.J., Nalls M.A., Keagle P., Rivera A.M., van Rheenen W., Murphy N.A., van Vugt J.J.F.A., Geiger J.T., Van der Spek R.A., Pliner H.A., Shankaracharya, Smith B.N., Marangi G., Topp S.D., Abramzon Y., Gkazi A.S., Eicher J.D., Kenna A., Logullo F.O., Simone I.L., Logroscino G., Salvi F., Bartolomei I., Borghero G., Murru M.R., Costantino E., Pani C., Puddu R., Caredda C., Piras V., Tranquilli S., Cuccu S., Corongiu D., Melis M., Milia A., Marrosu F., Marrosu M.G., Floris G., Cannas A., Capasso M., Caponnetto C., Mancardi G., Origone P., Mandich P., Conforti F.L., Cavallaro S., Mora G., Marinou K., Sideri R., Penco S., Mosca L., Lunetta C., Pinter G.L., Corbo M., Riva N., Carrera P., Volanti P., Mandrioli J., Fini N., Fasano A., Tremolizzo L., Arosio A., Ferrarese C., Trojsi F., Tedeschi G., Monsurro M.R., Piccirillo G., Femiano C., Ticca A., Ortu E., La Bella V., Spataro R., Colletti T., Sabatelli M., Zollino M., Conte A., Luigetti M., Lattante S., Santarelli M., Petrucci A., Pugliatti M., Pirisi A., Parish L.D., Occhineri P., Giannini F., Battistini S., Ricci C., Benigni M., Cau T.B., Loi D., Calvo A., Moglia C., Brunetti M., Barberis M., Restagno G., Casale F., Marrali G., Fuda G., Ossola I., Cammarosano S., Canosa A., Ilardi A., Manera U., Grassano M., Tanel R., Pisano F., Mazzini L., Messina S., D'Alfonso S., Corrado L., Ferrucci L., Harms M.B., Goldstein D.B., Shneider N.A., Goutman S.A., Simmons Z., Miller T.M., Chandran S., Pal S., Manousakis G., Appel S.H., Simpson E., Wang L., Baloh R.H., Gibson S.B., Bedlack R., Lacomis D., Sareen D., Sherman A., Bruijn L., Penny M., Moreno C.D.A.M., Kamalakaran S., Allen A.S., Boone B.E., Brown R.H., Carulli J.P., Chesi A., Chung W.K., Cirulli E.T., Cooper G.M., Couthouis J., Day-Williams A.G., Dion P.A., Gitler A.D., Glass J.D., Han Y., Harris T., Hayes S.D., Jones A.L., Keebler J., Krueger B.J., Lasseigne B.N., Levy S.E., Lu Y.-F., Maniatis T., McKenna-Yasek D., Myers R.M., Petrovski S., Pulst S.M., Raphael A.R., Ravits J.M., Ren Z., Rouleau G.A., Sapp P.C., Sims K.B., Staropoli J.F., Waite L.L., Wang Q., Wimbish J.R., Xin W.W., Phatnani H., Kwan J., Broach J., Arcila-Londono X., Lee E.B., Van Deerlin V.M., Fraenkel E., Ostrow L.W., Baas F., Zaitlen N., Berry J.D., Malaspina A., Fratta P., Cox G.A., Thompson L.M., Finkbeiner S., Dardiotis E., Hornstein E., MacGowan D.J.L., Heiman-Patterson T., Hammell M.G., Patsopoulos N.A., Dubnau J., Nath A., Musunuri R.L., Evani U.S., Abhyankar A., Zody M.C., Kaye J., Wyman S.K., LeNail A., Lima L., Rothstein J.D., Svendsen C.N., Van Eyk J.E., Maragakis N.J., Kolb S.J., Cudkowicz M., Baxi E., Benatar M., Taylor J.P., Wu G., Rampersaud E., Wuu J., Rademakers R., Zuchner S., Schule R., McCauley J., Hussain S., Cooley A., Wallace M., Clayman C., Barohn R., Statland J., Swenson A., Jackson C., Trivedi J., Khan S., Katz J., Jenkins L., Burns T., Gwathmey K., Caress J., McMillan C., Elman L., Pioro E.P., Heckmann J., So Y., Walk D., Maiser S., Zhang J., Silani V., Gellera C., Ratti A., Taroni F., Lauria G., Verde F., Fogh I., Tiloca C., Comi G.P., Soraru G., Cereda C., De Marchi F., Corti S., Ceroni M., Siciliano G., Filosto M., Inghilleri M., Peverelli S., Colombrita C., Poletti B., Maderna L., Del Bo R., Gagliardi S., Querin G., Bertolin C., Pensato V., Castellotti B., Camu W., Mouzat K., Lumbroso S., Corcia P., Meininger V., Besson G., Lagrange E., Clavelou P., Guy N., Couratier P., Vourch P., Danel V., Bernard E., Lemasson G., Laaksovirta H., Myllykangas L., Jansson L., Valori M., Ealing J., Hamdalla H., Rollinson S., Pickering-Brown S., Orrell R.W., Sidle K.C., Hardy J., Singleton A.B., Johnson J.O., Arepalli S., Polak M., Asress S., Al-Sarraj S., King A., Troakes C., Vance C., de Belleroche J., ten Asbroek A.L.M.A., Munoz-Blanco J.L., Hernandez D.G., Ding J., Gibbs J.R., Scholz S.W., Floeter M.K., Campbell R.H., Landi F., Bowser R., Kirby J., Pamphlett R., Gerhard G., Dunckley T.L., Brady C.B., Kowall N.W., Troncoso J.C., Le Ber I., Heiman-Patterson T.D., Kamel F., Van Den Bosch L., Strom T.M., Meitinger T., Shatunov A., Van Eijk K.R., de Carvalho M., Kooyman M., Middelkoop B., Moisse M., McLaughlin R.L., Van Es M.A., Weber M., Boylan K.B., Van Blitterswijk M., Morrison K.E., Basak A.N., Mora J.S., Drory V.E., Shaw P.J., Turner M.R., Talbot K., Hardiman O., Williams K.L., Fifita J.A., Nicholson G.A., Blair I.P., Esteban-Perez J., Garcia-Redondo A., Al-Chalabi A., Al Kheifat A., Andersen P.M., Chio A., Cooper-Knock J., Dekker A., Redondo A.G., Gotkine M., Hide W., Iacoangeli A., Kiernan M., Landers J.E., Mill J., Neto M.M., Pardina J.M., Newhouse S., Pinto S., Pulit S., Robberecht W., Shaw C., Sproviero W., Tazelaar G., Van Damme P., van den Berg L.H., van Vugt J., Veldink J.H., Zatz M., Bauer D.C., Twine N.A., Rogaeva E., Zinman L., Brice A., Feldman E.L., Ludolph A.C., Weishaupt J.H., Trojanowski J.Q., Stone D.J., Tienari P., Shaw C.E., Traynor B.J., ITALSGEN Consortium, Genomic Translation ALS Care GTAC, ALS Sequencing Consortium, NYGC ALS Consortium, Answer ALS Fdn, Clinical Res ALS Related Disorders, SLAGEN Consortium, French ALS Consortium, Project MinE ALS Sequencing Consor, Medical Research Council (MRC), ANS - Complex Trait Genetics, Human Genetics, ARD - Amsterdam Reproduction and Development, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Università cattolica del Sacro Cuore [Roma] (Unicatt), Centre référent Sclérose Latérale Amyotrophique [CHRU Montpellier] (SLA CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1), Lunar and Planetary Laboratory [Tucson] (LPL), University of Arizona, Università degli studi di Torino (UNITO), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), New York Genome Center [New York], New York Genome Center, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), St Jude Children's Research Hospital, Howard Hughes Medical Institute [Chevy Chase] (HHMI), Howard Hughes Medical Institute (HHMI), Centre de compétence de la Sclérose Latérale Amyotrophique [CHRU Tours] (SLA CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), University College of London [London] (UCL), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), King‘s College London, University of New Haven [Connecticut], Princeton University, Laboratoire de Biochimie [CHRU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Helmholtz-Zentrum München (HZM), University Medical Center [Utrecht], Deutsches Forschungszentrum für Künstliche Intelligenz GmbH = German Research Center for Artificial Intelligence (DFKI), Mayo Clinic [Jacksonville], Trinity College Dublin, Maurice Wohl Clinical Neuroscience Institut, Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Repositório da Universidade de Lisboa, Nicolas, A, Kenna, K, Renton, A, Ticozzi, N, Faghri, F, Chia, R, Dominov, J, Kenna, B, Nalls, M, Keagle, P, Rivera, A, van Rheenen, W, Murphy, N, van Vugt, J, Geiger, J, van der Spek, R, Pliner, H, Shankaracharya, N, Smith, B, Marangi, G, Topp, S, Abramzon, Y, Gkazi, A, Eicher, J, Kenna, A, Logullo, F, Simone, I, Logroscino, G, Salvi, F, Bartolomei, I, Borghero, G, Murru, M, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, M, Floris, G, Cannas, A, Capasso, M, Caponnetto, C, Mancardi, G, Origone, P, Mandich, P, Conforti, F, Cavallaro, S, Mora, G, Marinou, K, Sideri, R, Penco, S, Mosca, L, Lunetta, C, Pinter, G, Corbo, M, Riva, N, Carrera, P, Volanti, P, Mandrioli, J, Fini, N, Fasano, A, Tremolizzo, L, Arosio, A, Ferrarese, C, Trojsi, F, Tedeschi, G, Monsurrò, M, Piccirillo, G, Femiano, C, Ticca, A, Ortu, E, La Bella, V, Spataro, R, Colletti, T, Sabatelli, M, Zollino, M, Conte, A, Luigetti, M, Lattante, S, Santarelli, M, Petrucci, A, Pugliatti, M, Pirisi, A, Parish, L, Occhineri, P, Giannini, F, Battistini, S, Ricci, C, Benigni, M, Cau, T, Loi, D, Calvo, A, Moglia, C, Brunetti, M, Barberis, M, Restagno, G, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Canosa, A, Ilardi, A, Manera, U, Grassano, M, Tanel, R, Pisano, F, Mazzini, L, Messina, S, D'Alfonso, S, Corrado, L, Ferrucci, L, Harms, M, Goldstein, D, Shneider, N, Goutman, S, Simmons, Z, Miller, T, Chandran, S, Pal, S, Manousakis, G, Appel, S, Simpson, E, Wang, L, Baloh, R, Gibson, S, Bedlack, R, Lacomis, D, Sareen, D, Sherman, A, Bruijn, L, Penny, M, Moreno, C, Kamalakaran, S, Allen, A, Boone, B, Brown, R, Carulli, J, Chesi, A, Chung, W, Cirulli, E, Cooper, G, Couthouis, J, Day-Williams, A, Dion, P, Gitler, A, Glass, J, Han, Y, Harris, T, Hayes, S, Jones, A, Keebler, J, Krueger, B, Lasseigne, B, Levy, S, Lu, Y, Maniatis, T, McKenna-Yasek, D, Myers, R, Petrovski, S, Pulst, S, Raphael, A, Ravits, J, Ren, Z, Rouleau, G, Sapp, P, Sims, K, Staropoli, J, Waite, L, Wang, Q, Wimbish, J, Xin, W, Phatnani, H, Kwan, J, Broach, J, Arcila-Londono, X, Lee, E, Van Deerlin, V, Fraenkel, E, Ostrow, L, Baas, F, Zaitlen, N, Berry, J, Malaspina, A, Fratta, P, Cox, G, Thompson, L, Finkbeiner, S, Dardiotis, E, Hornstein, E, Macgowan, D, Heiman-Patterson, T, Hammell, M, Patsopoulos, N, Dubnau, J, Nath, A, Musunuri, R, Evani, U, Abhyankar, A, Zody, M, Kaye, J, Wyman, S, Lenail, A, Lima, L, Rothstein, J, Svendsen, C, Van Eyk, J, Maragakis, N, Kolb, S, Cudkowicz, M, Baxi, E, Benatar, M, Taylor, J, Wu, G, Rampersaud, E, Wuu, J, Rademakers, R, Züchner, S, Schule, R, Mccauley, J, Hussain, S, Cooley, A, Wallace, M, Clayman, C, Barohn, R, Statland, J, Swenson, A, Jackson, C, Trivedi, J, Khan, S, Katz, J, Jenkins, L, Burns, T, Gwathmey, K, Caress, J, Mcmillan, C, Elman, L, Pioro, E, Heckmann, J, So, Y, Walk, D, Maiser, S, Zhang, J, Silani, V, Gellera, C, Ratti, A, Taroni, F, Lauria, G, Verde, F, Fogh, I, Tiloca, C, Comi, G, Sorarù, G, Cereda, C, De Marchi, F, Corti, S, Ceroni, M, Siciliano, G, Filosto, M, Inghilleri, M, Peverelli, S, Colombrita, C, Poletti, B, Maderna, L, Del Bo, R, Gagliardi, S, Querin, G, Bertolin, C, Pensato, V, Castellotti, B, Camu, W, Mouzat, K, Lumbroso, S, Corcia, P, Meininger, V, Besson, G, Lagrange, E, Clavelou, P, Guy, N, Couratier, P, Vourch, P, Danel, V, Bernard, E, Lemasson, G, Laaksovirta, H, Myllykangas, L, Jansson, L, Valori, M, Ealing, J, Hamdalla, H, Rollinson, S, Pickering-Brown, S, Orrell, R, Sidle, K, Hardy, J, Singleton, A, Johnson, J, Arepalli, S, Polak, M, Asress, S, Al-Sarraj, S, King, A, Troakes, C, Vance, C, de Belleroche, J, ten Asbroek, A, Muñoz-Blanco, J, Hernandez, D, Ding, J, Gibbs, J, Scholz, S, Floeter, M, Campbell, R, Landi, F, Bowser, R, Kirby, J, Pamphlett, R, Gerhard, G, Dunckley, T, Brady, C, Kowall, N, Troncoso, J, Le Ber, I, Kamel, F, Van Den Bosch, L, Strom, T, Meitinger, T, Shatunov, A, Van Eijk, K, de Carvalho, M, Kooyman, M, Middelkoop, B, Moisse, M, Mclaughlin, R, Van Es, M, Weber, M, Boylan, K, Van Blitterswijk, M, Morrison, K, Basak, A, Mora, J, Drory, V, Shaw, P, Turner, M, Talbot, K, Hardiman, O, Williams, K, Fifita, J, Nicholson, G, Blair, I, Esteban-Pérez, J, García-Redondo, A, Al-Chalabi, A, Al Kheifat, A, Andersen, P, Chio, A, Cooper-Knock, J, Dekker, A, Redondo, A, Gotkine, M, Hide, W, Iacoangeli, A, Kiernan, M, Landers, J, Mill, J, Neto, M, Pardina, J, Newhouse, S, Pinto, S, Pulit, S, Robberecht, W, Shaw, C, Sproviero, W, Tazelaar, G, van Damme, P, van den Berg, L, van Eijk, K, van Es, M, Veldink, J, Zatz, M, Bauer, D, Twine, N, Rogaeva, E, Zinman, L, Brice, A, Feldman, E, Ludolph, A, Weishaupt, J, Trojanowski, J, Stone, D, Tienari, P, Chiò, A, Traynor, B, Nicolas, Aude, Kenna, Kevin P, Renton, Alan E, Ticozzi, Nicola, Faghri, Faraz, Chia, Ruth, Dominov, Janice A, Kenna, Brendan J, Nalls, Mike A, Keagle, Pamela, Rivera, Alberto M, van Rheenen, Wouter, Murphy, Natalie A, van Vugt, Joke J F A, Geiger, Joshua T, Van der Spek, Rick A, Pliner, Hannah A, Shankaracharya, Null, Smith, Bradley N, Marangi, Giuseppe, Topp, Simon D, Abramzon, Yevgeniya, Gkazi, Athina Soragia, Eicher, John D, Kenna, Aoife, Mora, Gabriele, Calvo, Andrea, Mazzini, Letizia, Riva, Nilo, Mandrioli, Jessica, Caponnetto, Claudia, Battistini, Stefania, Volanti, Paolo, La Bella, Vincenzo, Conforti, Francesca L, Borghero, Giuseppe, Messina, Sonia, Simone, Isabella L, Trojsi, Francesca, Salvi, Fabrizio, Logullo, Francesco O, D'Alfonso, Sandra, Corrado, Lucia, Capasso, Margherita, Ferrucci, Luigi, Logullo, Fo, Murru, Mr, Marrosu, Mg, Conforti, Fl, Pinter, Gl, Tedeschi, Gioacchino, Monsurrò, Maria Rosaria, Parish, Ld, Cau, Tb, Moreno, Cristiane de Araujo Martin, Kamalakaran, Sitharthan, Goldstein, David B, Gitler, Aaron D, Harris, Tim, Myers, Richard M, Phatnani, Hemali, Musunuri, Rajeeva Lochan, Evani, Uday Shankar, Abhyankar, Avinash, Zody, Michael C, Kaye, Julia, Finkbeiner, Steven, Wyman, Stacia K, Lenail, Alex, Lima, Leandro, Fraenkel, Ernest, Svendsen, Clive N, Thompson, Leslie M, Van Eyk, Jennifer E, Berry, James D, Miller, Timothy M, Kolb, Stephen J, Cudkowicz, Merit, Baxi, Emily, Benatar, Michael, Taylor, J Paul, Rampersaud, Evadnie, Wu, Gang, Wuu, Joanne, Lauria, Giuseppe, Verde, Federico, Fogh, Isabella, Tiloca, Cinzia, Comi, Giacomo P, Sorarù, Gianni, Cereda, Cristina, Corcia, Philippe, Laaksovirta, Hannu, Myllykangas, Liisa, Jansson, Lilja, Valori, Miko, Ealing, John, Hamdalla, Hisham, Rollinson, Sara, Pickering-Brown, Stuart, Orrell, Richard W, Sidle, Katie C, Malaspina, Andrea, Hardy, John, Singleton, Andrew B, Johnson, Janel O, Arepalli, Sampath, Sapp, Peter C, McKenna-Yasek, Diane, Polak, Meraida, Asress, Seneshaw, Al-Sarraj, Safa, King, Andrew, Troakes, Claire, Vance, Caroline, de Belleroche, Jacqueline, Baas, Frank, Ten Asbroek, Anneloor L M A, Muñoz-Blanco, José Lui, Hernandez, Dena G, Ding, Jinhui, Gibbs, J Raphael, Scholz, Sonja W, Floeter, Mary Kay, Campbell, Roy H, Landi, Francesco, Bowser, Robert, Pulst, Stefan M, Ravits, John M, Macgowan, Daniel J L, Kirby, Janine, Pioro, Erik P, Pamphlett, Roger, Broach, Jame, Gerhard, Glenn, Dunckley, Travis L, Brady, Christopher B, Kowall, Neil W, Troncoso, Juan C, Le Ber, Isabelle, Mouzat, Kevin, Lumbroso, Serge, Heiman-Patterson, Terry D, Kamel, Freya, Van Den Bosch, Ludo, Baloh, Robert H, Strom, Tim M, Meitinger, Thoma, Shatunov, Aleksey, Van Eijk, Kristel R, de Carvalho, Mamede, Kooyman, Maarten, Middelkoop, Ba, Moisse, Matthieu, Mclaughlin, Russell L, Van Es, Michael A, Weber, Marku, Boylan, Kevin B, Van Blitterswijk, Marka, Rademakers, Rosa, Morrison, Karen E, Basak, A Nazli, Mora, Jesús S, Drory, Vivian E, Shaw, Pamela J, Turner, Martin R, Talbot, Kevin, Hardiman, Orla, Williams, Kelly L, Fifita, Jennifer A, Nicholson, Garth A, Blair, Ian P, Rouleau, Guy A, Esteban-Pérez, Jesú, García-Redondo, Alberto, Al-Chalabi, Ammar, Rogaeva, Ekaterina, Zinman, Lorne, Ostrow, Lyle W, Maragakis, Nicholas J, Rothstein, Jeffrey D, Simmons, Zachary, Cooper-Knock, Johnathan, Brice, Alexi, Goutman, Stephen A, Feldman, Eva L, Gibson, Summer B, Taroni, Franco, Ratti, Antonia, Gellera, Cinzia, Van Damme, Philip, Robberecht, Wim, Fratta, Pietro, Sabatelli, Mario, Lunetta, Christian, Ludolph, Albert C, Andersen, Peter M, Weishaupt, Jochen H, Camu, William, Trojanowski, John Q, Van Deerlin, Vivianna M, Brown, Robert H, van den Berg, Leonard H, Veldink, Jan H, Harms, Matthew B, Glass, Jonathan D, Stone, David J, Tienari, Pentti, Silani, Vincenzo, Chiò, Adriano, Shaw, Christopher E, Traynor, Bryan J, Landers, John E, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
Male, Als gene, Genome-wide association study, FAMILIAL ALS, ALS, axonal transport, cargo, GWAS, KIF5A, WES, WGS, 0302 clinical medicine, 80 and over, Psychology, Aetiology, Aged, 80 and over, 0303 health sciences, French ALS Consortium, Kinesin, KINESIN HEAVY-CHAIN, Cognitive Sciences, Human, Hereditary spastic paraplegia, Neuroscience(all), Single-nucleotide polymorphism, TARGETED DISRUPTION, Article, 03 medical and health sciences, Genetics, Humans, Amino Acid Sequence, Loss function, Aged, HEXANUCLEOTIDE REPEAT, Neuroscience (all), MUTATIONS, Amyotrophic Lateral Sclerosis, 3112 Neurosciences, 1702 Cognitive Science, medicine.disease, ITALSGEN Consortium, Answer ALS Foundation, 030104 developmental biology, ALS Sequencing Consortium, Human medicine, 1109 Neurosciences, 030217 neurology & neurosurgery, 0301 basic medicine, [SDV]Life Sciences [q-bio], Kinesins, Neurodegenerative, Genetic analysis, Genome, AMYOTROPHIC-LATERAL-SCLEROSIS, 3124 Neurology and psychiatry, Cohort Studies, Pathogenesis, Loss of Function Mutation, Missense mutation, 2.1 Biological and endogenous factors, Amyotrophic lateral sclerosis, NYGC ALS Consortium, General Neuroscience, ALS, axonal transport, cargo, GWAS, KIF5A, WES, WGS, Middle Aged, Phenotype, Settore MED/26 - NEUROLOGIA, Neurological, Project MinE ALS Sequencing Consortium, Female, Adult, Biology, GENOTYPE IMPUTATION, Genome-Wide Association Study, Young Adult, NO, Rare Diseases, medicine, SLAGEN Consortium, Gene, 030304 developmental biology, Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium, Neurology & Neurosurgery, Human Genome, Neurosciences, AXONAL-TRANSPORT, Brain Disorders, Family member, DNA-DAMAGE, MOTOR-NEURONS, 3111 Biomedicine, Cohort Studie, Genomic Translation for ALS Care (GTAC) Consortium, Amyotrophic Lateral Sclerosi
Abstract

© 2018 Elsevier Inc., To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.

Published
2018
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2. Genetic analysis of neurodegenerative diseases in a pathology cohort

Author

Cornelis Blauwendraat, Olga Pletnikova, Joshua T. Geiger, Natalie A. Murphy, Yevgeniya Abramzon, Gay Rudow, Adamantios Mamais, Marya S. Sabir, Barbara Crain, Sarah Ahmed, Liana S. Rosenthal, Catherine C. Bakker, Faraz Faghri, Ruth Chia, Jinhui Ding, Ted M. Dawson, Alexander Pantelyat, Marilyn S. Albert, Mike A. Nalls, Susan M. Resnick, Luigi Ferrucci, Mark R. Cookson, Argye E. Hillis, Juan C. Troncoso, and Sonja W. Scholz

Subjects
Male, 0301 basic medicine, Aging, Genotyping Techniques, Disease, Biology, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Genetic analysis, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, C9orf72, PSEN1, medicine, Humans, Genotyping, Genetic Association Studies, Aged, Aged, 80 and over, Genetics, DNA Repeat Expansion, C9orf72 Protein, General Neuroscience, Neurodegeneration, Neurodegenerative Diseases, Middle Aged, medicine.disease, LRRK2, High-Throughput Screening Assays, 030104 developmental biology, Molecular Diagnostic Techniques, Mutation, Cohort, Female, Neurology (clinical), Geriatrics and Gerontology, 030217 neurology & neurosurgery, Developmental Biology
Abstract

Molecular genetic research provides unprecedented opportunities to examine genotype-phenotype correlations underlying complex syndromes. To investigate pathogenic mutations and genotype-phenotype relationships in diverse neurodegenerative conditions, we performed a rare variant analysis of damaging mutations in autopsy-confirmed neurodegenerative cases from the Johns Hopkins Brain Resource Center (n = 1243 patients). We used NeuroChip genotyping and C9orf72 hexanucleotide repeat analysis to rapidly screen our cohort for disease-causing mutations. In total, we identified 42 individuals who carried a pathogenic mutation in LRRK2, GBA, APP, PSEN1, MAPT, GRN, C9orf72, SETX, SPAST, or CSF1R, and we provide a comprehensive description of the diverse clinicopathological features of these well-characterized cases. Our study highlights the utility of high-throughput genetic screening arrays to establish a molecular diagnosis in individuals with complex neurodegenerative syndromes, to broaden disease phenotypes and to provide insights into unexpected disease associations.

Published
2019
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3. To Dement or Not to Dement, That Is the Question

Author

Yevgeniya Abramzon and Bryan J. Traynor

Subjects
Genetic Markers, Male, 0301 basic medicine, medicine.medical_specialty, Apolipoprotein E2, Genetic counseling, Neurogenetics, Disease, Biology, Article, Cohort Studies, 03 medical and health sciences, Apolipoproteins E, 0302 clinical medicine, medicine, Dementia, Humans, Risk factor, Amyotrophic lateral sclerosis, Psychiatry, Aged, C9orf72 Protein, Amyotrophic Lateral Sclerosis, Proteins, Middle Aged, medicine.disease, Minor allele frequency, 030104 developmental biology, Italy, Frontotemporal Dementia, Female, Neurology (clinical), 030217 neurology & neurosurgery, Frontotemporal dementia, Clinical psychology
Abstract

Until a decade ago, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) were considered to be distinct neurodegenerative conditions: one was clinically characterized by paralysis and the other by cognitive dysfunction. Epidemiologic, clinical, and neuropathologic data now make it clear that the 2 conditions form a spectrum of disease.1,2 Genetic studies have played a central role in determining the cellular mechanisms underlying the overlap of ALS and FTD. In particular, the pathogenic repeat expansion in the C9ORF72 (Entrez GeneID: 203228) gene was found to account for a large percentage of cases of ALS-FTD.3,4 Despite theseadvances, the relationshipbetweenALSand dementia is only partially resolved. A particularly troubling problem is thatwedonotunderstandwhy somepatientswith ALSdevelopdementiawhile others donot, evenwhen thepatients are close family relatives carrying the same genemutation. Environment and lifestyle factors almost certainly play a role indetermining this outcome.Nevertheless, efforts have focused largely on identifying the genetic factors that lead to dementia in ALS, in part because modern genomic technologies allow these hypotheses to be tested relatively easily. Genetic variants that determine whether an individual carrying the C9ORF72 repeat expansion will present with ALS or FTD have already been reported. For example, homozygosity for the minor allele of rs3173615 in TMEM106B (Entrez GeneID: 54664) protects carriers of the repeat expansion from developing FTD but not from developing ALS.5 These studies focus largely on predicting whether the initial presenting features would be muscle paralysis or frontal lobe dysfunction. In contrast, Chio and colleagues6 followed a cohort of patients with ALS over time to identify those who developed dementia during the course of their illness and those who did not. Using this information, they then tested whether APOE (Entrez GeneID: 348) genotype influenced this outcome and found that the presence of an APOE e2 allele increased the risk of FTD by nearly 3-fold. This is not the first time that APOE has been studied in patients with ALS. Previous studies, however, focused on whether this allele increased the risk of developing ALS or altered the age at onset; results were either negative or unconvincing.7-9 The innovative feature of the study by Chio et al6 is that they evaluated the effect of APOE on longitudinal outcome, not just presentation of disease. This is a subtle but crucially important distinction, as their results show. The most obvious strength of the study by Chio et al6 lies in their use of a population-based, longitudinal registry of patients with ALS, without which they would not have been able to evaluate long-term cognitive status. This Northern Italian registry has been in existence for 20 years,10 and Chio et al6 illustrate how such large-scale data collection efforts can be leveraged to answer important questions in the field. The recognition of APOE as a risk factor for dementia in ALS has immediate implications for clinical care. Knowing that an individual is likely to develop dementia will help prioritize the establishment of a living will at a time when the patient is still able to participate and will help caregivers cope with the patient’s behavioral changes arising from the illness. It will also facilitate genetic counseling of other family members. In addition, the identification of the role of APOE has broader implications for how we think about and perceive neurodegeneration. As neurologists, we are trained to diagnose patients according to their presenting symptoms. This paradigm retains obvious clinical utility, but it is increasingly recognized that neurodegeneration does not respect these silos and is more dynamic in nature. Pathologists frequently observe multiple types of inclusions in brains undergoing autopsy,11 and geneticists are increasingly reporting that mutations in a gene that causes one form of neurodegeneration increase risk in other forms of neurodegeneration.12,13 The study by Chio et al6 is certainly a good step forward in our understanding of the genetic architecture underlying ALS and dementia. Like all good science, however, it raises more questions than it answers. For example, do patients with ALS who are carrying the APOE risk allele have more amyloid deposition or are other protein species involved? Why is the APOE e2 allele a risk factor for FTD, when it is thought to be protective in other neurodegenerative diseases? Why do some patients carrying the APOE risk factor not develop dementia?14 Does this finding suggest the existence of additional risk factors or even protective factors elsewhere in the genome? Genome-wide studies would be the ideal way to search for such loci, but such studies will be challenging owing to the multiple testing involved, the requirement for large sample sizes, and the difficulty in interpreting how these multiple risk factors are operating within the central nervous system. This is a complex problem indeed but an important one to address if we are to arrive at a better understanding of neurodegeneration. Therein lies the rub.

Published
2016

4. Exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease

Author

Javier Simón-Sánchez, Janel O. Johnson, Andrew B. Singleton, Peter E. Clayton, Francesco Muntoni, Sampath Arepalli, J. Raphael Gibbs, J. Andoni Urtizberea, Henry Houlden, A. Reghan Foley, Amelie Pandraud, André Mégarbané, Dena G. Hernandez, Mary M. Reilly, and Yevgeniya Abramzon

Subjects
Male, Genotype, Hearing Loss, Sensorineural, Bulbar Palsy, Progressive, Biology, medicine.disease_cause, Polymorphism, Single Nucleotide, Receptors, G-Protein-Coupled, Gene Frequency, Brown–Vialetto–Van Laere syndrome, medicine, Humans, Gene family, Exome, Disease-causing Mutation, Motor Neuron Disease, Child, Alleles, Exome sequencing, Genetics, Mutation, Original Articles, medicine.disease, Pedigree, Riboflavin transport, Child, Preschool, Female, Neurology (clinical)
Abstract

Brown-Vialetto-Van Laere syndrome was first described in 1894 as a rare neurodegenerative disorder characterized by progressive sensorineural deafness in combination with childhood amyotrophic lateral sclerosis. Mutations in the gene, SLC52A3 (formerly C20orf54), one of three known riboflavin transporter genes, have recently been shown to underlie a number of severe cases of Brown-Vialetto-Van Laere syndrome; however, cases and families with this disease exist that do not appear to be caused by SLC52A3 mutations. We used a combination of linkage and exome sequencing to identify the disease causing mutation in an extended Lebanese Brown-Vialetto-Van Laere kindred, whose affected members were negative for SLC52A3 mutations. We identified a novel mutation in a second member of the riboflavin transporter gene family (gene symbol: SLC52A2) as the cause of disease in this family. The same mutation was identified in one additional subject, from 44 screened. Within this group of 44 patients, we also identified two additional cases with SLC52A3 mutations, but none with mutations in the remaining member of this gene family, SLC52A1. We believe this strongly supports the notion that defective riboflavin transport plays an important role in Brown-Vialetto-Van Laere syndrome. Initial work has indicated that patients with SLC52A3 defects respond to riboflavin treatment clinically and biochemically. Clearly, this makes an excellent candidate therapy for the SLC52A2 mutation-positive patients identified here. Initial riboflavin treatment of one of these patients shows promising results.

Published
2012
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5. A genome-wide association study of myasthenia gravis

Author

Sampath Arepalli, Gabriella Restagno, David P. Richman, Julaine Florence, Michael Benatar, Sean Chong, Miriam Freimer, Henry J. Kaminski, Sonja W. Scholz, Robert M. Pascuzzi, Andrea M. Corse, Carlo Provenzano, Bryan J. Traynor, Emanuela Bartoccioni, Janel O. Johnson, Srikanth Muppidi, Daniel B. Drachman, Gil I. Wolfe, Mike A. Nalls, Janice M. Massey, Adriano Chiò, Manisha Chopra, Derrick Blackmore, Flavia Scuderi, Mamatha Pasnoor, Roberta Ricciardi, Joel Oger, J. Raphael Gibbs, April McVey, Edoardo Errichiello, Charlie Wulf, Theresa Jiwa, Mazen M. Dimachkie, Hannah A. Pliner, Richard J. Barohn, Michael W. Nicolle, Zaeem A. Siddiqi, Giuseppe Marangi, Amelia Evoli, Vinay Chaudhry, James F. Howard, Wilma J. Koopman, Bernadette Lipscomb, Mark Macek, Michelangelo Maestri, Dena G. Hernandez, Alan Pestronk, Julie Rowin, John T. Kissel, Donald B. Sanders, Mario Sabatelli, Michelle M. Mezei, Alan E. Renton, Yevgeniya Abramzon, and Aimee Soloway

Subjects
Male, Genome-wide association study, Settore MED/03 - GENETICA MEDICA, Settore MED/05 - PATOLOGIA CLINICA, Gene Frequency, 2.1 Biological and endogenous factors, GWAS, CTLA-4 Antigen, Aetiology, Age of Onset, Single Nucleotide, Middle Aged, Cohort, Cognitive Sciences, Female, medicine.symptom, Adult, Weakness, medicine.medical_specialty, Neuromuscular disease, Genotype, Clinical Sciences, Miastenia gravis, Single-nucleotide polymorphism, Autoimmune Disease, Polymorphism, Single Nucleotide, HLA-DQ alpha-Chains, Rare Diseases, Arts and Humanities (miscellaneous), Clinical Research, Internal medicine, Myasthenia Gravis, medicine, Genetics, Humans, Genetic Predisposition to Disease, Polymorphism, Neurology & Neurosurgery, business.industry, Human Genome, Case-control study, Neurosciences, Odds ratio, medicine.disease, Myasthenia gravis, United States, Case-Control Studies, Immunology, Genome-Wide Association Study, Neurology (clinical), business
Abstract

Importance Myasthenia gravis is a chronic, autoimmune, neuromuscular disease characterized by fluctuating weakness of voluntary muscle groups. Although genetic factors are known to play a role in this neuroimmunological condition, the genetic etiology underlying myasthenia gravis is not well understood. Objective To identify genetic variants that alter susceptibility to myasthenia gravis, we performed a genome-wide association study. Design, Setting, and Participants DNA was obtained from 1032 white individuals from North America diagnosed as having acetylcholine receptor antibody–positive myasthenia gravis and 1998 race/ethnicity-matched control individuals from January 2010 to January 2011. These samples were genotyped on Illumina OmniExpress single-nucleotide polymorphism arrays. An independent cohort of 423 Italian cases and 467 Italian control individuals were used for replication. Main Outcomes and Measures We calculated P values for association between 8 114 394 genotyped and imputed variants across the genome and risk for developing myasthenia gravis using logistic regression modeling. A threshold P value of 5.0 × 10 −8 was set for genome-wide significance after Bonferroni correction for multiple testing. Results In the overall case-control cohort, we identified association signals at CTLA4 (rs231770; P = 3.98 × 10 −8 ; odds ratio, 1.37; 95% CI, 1.25-1.49), HLA-DQA1 (rs9271871; P = 1.08 × 10 −8 ; odds ratio, 2.31; 95% CI, 2.02 - 2.60), and TNFRSF11A (rs4263037; P = 1.60 × 10 −9 ; odds ratio, 1.41; 95% CI, 1.29-1.53). These findings replicated for CTLA4 and HLA-DQA1 in an independent cohort of Italian cases and control individuals. Further analysis revealed distinct, but overlapping, disease-associated loci for early- and late-onset forms of myasthenia gravis. In the late-onset cases, we identified 2 association peaks: one was located in TNFRSF11A (rs4263037; P = 1.32 × 10 −12 ; odds ratio, 1.56; 95% CI, 1.44-1.68) and the other was detected in the major histocompatibility complex on chromosome 6p21 ( HLA-DQA1 ; rs9271871; P = 7.02 × 10 −18 ; odds ratio, 4.27; 95% CI, 3.92-4.62). Association within the major histocompatibility complex region was also observed in early-onset cases ( HLA-DQA1 ; rs601006; P = 2.52 × 10 −11 ; odds ratio, 4.0; 95% CI, 3.57-4.43), although the set of single-nucleotide polymorphisms was different from that implicated among late-onset cases. Conclusions and Relevance Our genetic data provide insights into aberrant cellular mechanisms responsible for this prototypical autoimmune disorder. They also suggest that clinical trials of immunomodulatory drugs related to CTLA4 and that are already Food and Drug Administration approved as therapies for other autoimmune diseases could be considered for patients with refractory disease.

Published
2015

6. Large C9orf72 repeat expansions are not a common cause of Parkinson’s disease

Author

Andrew B. Singleton, Margaux F. Keller, Elisa Majounie, Bryan J. Traynor, Yevgeniya Abramzon, and Alan E. Renton

Subjects
Adult, Male, Aging, Parkinson's disease, Adolescent, Disease, Bioinformatics, Article, Cohort Studies, Young Adult, C9orf72, medicine, Humans, Amyotrophic lateral sclerosis, Age of Onset, Child, Aged, Aged, 80 and over, DNA Repeat Expansion, C9orf72 Protein, business.industry, General Neuroscience, Amyotrophic Lateral Sclerosis, Proteins, Parkinson Disease, Middle Aged, medicine.disease, Frontotemporal Dementia, Female, Neurology (clinical), Geriatrics and Gerontology, Age of onset, business, Neuroscience, Developmental Biology, Frontotemporal dementia
Abstract

The concept of a pathological overlap between neurodegenerative disorders is gaining momentum. We sought to determine the contribution of C9orf72 repeat expansions, recently discovered as a cause of frontotemporal dementia and amyotrophic lateral sclerosis, in a large number of Parkinson's disease patients. No large expansions were identified in our cohort.

Published
2012

7. Repeat expansion in C9ORF72 in Alzheimer's disease

Author

Olga Pletnikova, Susan Spear Bassett, John Hardy, Andrew B. Singleton, Juan C. Troncoso, Rodney T. Perry, Elisa Majounie, Bryan J. Traynor, Alan E. Renton, and Yevgeniya Abramzon

Subjects
Male, Pathology, medicine.medical_specialty, Article, C9orf72, Alzheimer Disease, medicine, Humans, Amyotrophic lateral sclerosis, Age of Onset, Diagnostic Errors, Aged, Aged, 80 and over, DNA Repeat Expansion, C9orf72 Protein, business.industry, Proteins, General Medicine, Middle Aged, medicine.disease, Frontotemporal Dementia, Female, Age of onset, Alzheimer's disease, Trinucleotide repeat expansion, business, Chromosomes, Human, Pair 9, Frontotemporal dementia
Abstract

A hexanucleotide repeat expansion in the gene C9ORF72 has been implicated in the development of amyotrophic lateral sclerosis and frontotemporal dementia. The variant has also been found in a small percentage of patients with probable late-onset Alzheimer's disease.

Published
2012

8. FUS mutations in sporadic amyotrophic lateral sclerosis

Author

Amelia Conte, Mario Sabatelli, Maria Rosaria Monsurrò, Travis Dunckley, Ilaria Bartolomei, Yevgeniya Abramzon, Gabriella Restagno, Kalliopi Marinou, Shiao Lin Lai, Patrizia Sola, Gioacchino Tedeschi, Fabio Giannini, Mark R. Cookson, Allissa Dillman, Giovanni Luigi Mancardi, Fabrizio Salvi, Rossella Spataro, Dietrich A. Stephan, Gabriele Mora, Claudia Caponnetto, Adriano Chiò, Bryan J. Traynor, Jessica Mandrioli, Andrea Calvo, Stefania Battistini, Federica Lombardo, Jennifer C. Schymick, Lai, Sl, Abramzon, Y, Schymick, Jc, Stephan, Da, Dunckley, T, Dillman, A, Cookson, M, Calvo, A, Battistini, S, Giannini, F, Caponnetto, C, Mancardi, Gl, Spataro, R, Monsurro', Maria Rosaria, Tedeschi, Gioacchino, Marinou, K, Sabatelli, M, Conte, A, Mandrioli, J, Sola, P, Salvi, F, Bartolomei, I, Lombardo, F, the ITALSGEN, Consortium, Mora, G, Restagno, G, Chiò, A, Traynor, B. J., Lai, SL, Schymick, JC, Stephan, DA, Dunckley,T, Mancardi, GL, Monsurro, MR, Tedeschi, G, ITALSGEN Consortium, and Traynor, BJ

Subjects
Adult, Male, Aging, Amyotrophic lateral sclerosis, FUS, Italy, Sporadic disease, United States of America, Adolescent, Genotype, sporadic patients, DNA Mutational Analysis, ALS, FUS mutations, Biology, medicine.disease_cause, Article, Pathogenesis, Exon, Young Adult, medicine, Humans, Child, Gene, Aged, Genetics, Aged, 80 and over, Mutation, General Neuroscience, Amyotrophic Lateral Sclerosis, amyotrophic lateral sclerosis, FUS, genetics, Exons, Middle Aged, medicine.disease, United States, Settore MED/26 - NEUROLOGIA, RNA-Binding Protein FUS, Female, Neurology (clinical), Geriatrics and Gerontology, Developmental Biology
Abstract

Mutations in the FUS gene have recently been described as a cause of familial amyotrophic lateral sclerosis (ALS), but their role in the pathogenesis of sporadic ALS is unclear. We undertook mutational screening of all coding exons of FUS in 228 sporadic ALS cases, and, as previous reports suggest that exon 15 represents a mutational hotspot, we sequenced this exon in an additional 1295 sporadic cases. Six variants in six different cases were found, indicating that FUS mutations can underlie apparently sporadic ALS, but account for less than 1% of this form of disease. © 2010 .

Published
2011

9. Valosin-containing protein (VCP) mutations in sporadic amyotrophic lateral sclerosis

Author

Janel O. Johnson, Jessica Mandrioli, Andrea Calvo, Gabriella Restagno, Michael Benatar, J.P. Taylor, Yevgeniya Abramzon, Bryan J. Traynor, Adriano Chiò, Gabriele Mora, Maura Brunetti, and Sonja W. Scholz

Subjects
Male, amyotrophic lateral sclerosis, Aging, Pathology, medicine.medical_specialty, valosin containing protein, Valosin-containing protein, DNA Mutational Analysis, Cell Cycle Proteins, Disease, Amyotrophic lateral sclerosis, Mutations, Sporadic disease, medicine.disease_cause, Article, Pathogenesis, medicine, Humans, genetics, Gene, Aged, Adenosine Triphosphatases, Mutation, biology, General Neuroscience, Middle Aged, medicine.disease, United States, Italy, biology.protein, Female, Neurology (clinical), Lower motor neuron signs, Geriatrics and Gerontology, Developmental Biology
Abstract

We recently reported that mutations in the valosin-containing protein (VCP) gene are a cause of 1%–2% of familial amyotrophic lateral sclerosis (ALS) cases, but their role in the pathogenesis of sporadic ALS is unclear. We undertook mutational screening of VCP in 701 sporadic ALS cases. Three pathogenic variants (p.Arg159Cys, p.Asn387Thr, and p.R662C) were found in three U.S. cases, each of whom presented with progressive upper and lower motor neuron signs consistent with definite ALS by El Escorial diagnostic criteria. Our data indicate that VCP mutations may underlie apparently sporadic ALS but account for

Published
2012
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10. C9ORF72 hexanucleotide repeat expansions in the Italian sporadic ALS population

Author

Mario, Sabatellia, Francesca Luisa Conforti, Marcella, Zollinoc, Gabriele, Morad, Maria Rosaria Monsurrò, Paolo, Volanti, Kalliopi, Marinoud, Fabrizio, Salvig, Massimo, Corbo, Fabio, Giannini, Stefania, Battistini, Silvana, Penco, Christian, Lunetta, Aldo, Quattrone, Antonio, Gambardella, Giancarlo, Logroscino, Isabella, Simone, Ilaria, Bartolomei, Fabrizio, Pisano, Gioacchino, Tedeschi, Amelia, Conte, Rossella, Spataro, Vincenzo La Bella, Claudia, Caponnetto, Gianluigi, Mancardi, Paola, Mandich, Patrizia, Sola, Jessica, Mandrioli, Renton, Alan E., Elisa, Majounie, Yevgeniya, Abramzon, Francesco, Marrosu, Maria Giovanna Marrosu, Maria Rita Murru, Maria Alessandra Sotgiu, Maura, Pugliatti, Rodolico, Carmelo, the ITALSGEN Consortium: Stefania Cammarosano, Giuseppe, Fuda, Antonio, Canosa, Sara, Gallo, Laura, Papetti, Giuseppe Lauria Pinter, Marco, Luigetti, Serena, Lattante, Giuseppe, Marangi, Tiziana, Colletti, Claudia, Ricci, Paola, Origone, Gianluca, Floris, Antonino, Cannas, Valeria, Piras, Emanuela, Costantino, Carla, Pani, Parish, Leslie D., Paola, Cossu, Giuliana, Solinas, Lucia, Ulgheri, Anna, Ticca, Francesco, Izzo, Anna, Laiola, Francesca, Trojsi, Portaro, Simona, William, Sproviero, Cristina, Moglia, Andrea, Calvo, Irene, Ossola, Maura, Brunetti, Traynor, Bryan J., Giuseppe, Borghero, Gabriella, Restagno, Adriano, Chiò, Sabatelli, M, Conforti, Fl, Zollino, M, Mora, G, Monsurro', Maria Rosaria, Volanti, P, Marinou, K, Salvi, F, Corbo, M, Giannini, F, Battistini, S, Penco, S, Lunetta, C, Quattrone, A, Gambardella, A, Logroscino, G, Simone, I, Bartolomei, I, Pisano, F, Tedeschi, Gioacchino, Conte, A, Spataro, R, La Bella, V, Caponnetto, C, Mancardi, G, Mandich, P, Sola, P, Mandrioli, J, Renton, Ae, Majounie, E, Abramzon, Y, Marrosu, F, Marrosu, Mg, Murru, Mr, Sotgiu, Ma, Pugliatti, M, Rodolico, C, ITALSGEN Consortium: Cammarosano, Stefania, Fuda, Giuseppe, Canosa, Antonio, Gallo, Sara, Papetti, Laura, Lauria Pinter, Giuseppe, Luigetti, Marco, Lattante, Serena, Marangi, Giuseppe, Colletti, Tiziana, Ricci, Claudia, Origone, Paola, Floris, Gianluca, Cannas, Antonino, Piras, Valeria, Costantino, Emanuela, Pani, Carla, Parish, Leslie D, Cossu, Paola, Solinas, Giuliana, Lucia, U. l. g. h. e. r. i., Ticca, Anna, Izzo, Francesco, Laiola, Anna, Trojsi, Francesca, Portaro, Simona, Sproviero, William, Moglia, C, Calvo, A, Ossola, I, Brunetti, M, Traynor, Bj, Borghero, G, Restagno, G, Chiò, A., Sabatelli, M., Conforti, F., Zollino, M., Mora, G., Monsurrò, M., Volanti, P., Marinou, K., Salvi, F., Corbo, M., Giannini, F., Battistini, S., Penco, S., Lunetta, C., Quattrone, A., Gambardella, A., Logroscino, G., Simone, I., Bartolomei, I., Pisano, F., Tedeschi, G., Conte, A., Spataro, R., LA BELLA, V., Caponnetto, C., Mancardi, G., Mandich, P., Sola, P., Mandrioli, J., Renton, A., Majounie, E., Abramzon, Y., Marrosu, F., Marrosu, M., Murru, M., Sotgiu, M., Pugliatti, M., Rodolico, C., Italsgen, C., Moglia, C., Calvo, A., Ossola, I., Brunetti, M., Traynor, B., Borghero, G., and Restagno, G.

Subjects
Male, Aging, Survival, Pedigree chart, Settore MED/03 - GENETICA MEDICA, Repetitive Sequences, 0302 clinical medicine, C9orf72, Polymorphism (computer science), Risk Factors, Prevalence, Amyotrophic lateral sclerosis, Genetics, 0303 health sciences, education.field_of_study, General Neuroscience, Single Nucleotide, Middle Aged, 3. Good health, Settore MED/26 - NEUROLOGIA, Italy, Female, Settore MED/26 - Neurologia, Frontotemporal dementia, Genetic Markers, Population, C9ORF72, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, medicine, Humans, Genetic Predisposition to Disease, Polymorphism, education, amyotrophic lateral sclerosis, C9orf672, frontotemporal dementia, survival, Amyotrophic lateral sclerosi, 030304 developmental biology, Repetitive Sequences, Nucleic Acid, sporadic, C9orf72 Protein, Nucleic Acid, Amyotrophic lateral sclerosis, C9ORF72, Frontotemporal dementia, Survival, Genetic Variation, Proteins, medicine.disease, Settore BIO/18 - Genetica, Neurology (clinical), Geriatrics and Gerontology, ALS, Trinucleotide repeat expansion, 030217 neurology & neurosurgery, Developmental Biology
Abstract

It has been recently reported that a large proportion of patients with familial amyotrophic lateral sclerosis (familial ALS) and frontotemporal dementia (FTD) are associated with a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72. We have assessed 1,757 Italian sporadic ALS cases, 133 from Sardinia, 101 from Sicily, and 1,523 from mainland Italy. Sixty (3.7%) of 1,624 mainland Italians and Sicilians and 9 (6.8%) of the 133 Sardinian sporadic ALS cases carried the pathogenic repeat expansion. None of the 619 regionally-matched control samples (1,238 chromosomes) carried the expansion. Twenty-five cases (36.2%) had behavioral FTD in addition to ALS. FTD or unspecified dementia was also detected in 19 pedigrees (27.5%) in first-degree relatives of ALS patients. Cases carrying the C9ORF72 hexanucleotide expansion survived one year less than cases who did not carry this mutation. In conclusion, we found that C9ORF72 hexanucloetide repeat expansions represents a sizeable proportion of apparent sporadic ALS in the Italian and Sardinian population, representing by far the commonest mutation in Italy and the second more common in Sardinia.

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