Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12530/37356
Title: Genome-wide Analyses Identify KIF5A as a Novel ALS Gene.
Authors: 
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
Moreno, Cristiane de Araujo Martins
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 Luis
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, James
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, Thomas
Shatunov, Aleksey
Van Eijk, Kristel R
de Carvalho, Mamede
Kooyman, Maarten
Middelkoop, Bas
Moisse, Matthieu
McLaughlin, Russell L
Van Es, Michael A
Weber, Markus
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, Jesús
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, Alexis
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
Keywords: 
Issue Date: 21-Mar-2018
Citation: Neuron.2018 Mar;(97)6:1268-1283.e6
Abstract: 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.
PMID: 29566793
URI: https://hdl.handle.net/20.500.12530/37356
Rights: openAccess
Appears in Collections:Fundaciones e Institutos de Investigación > IIS H. General U. Gregorio Marañón > Artículos

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