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Neuron · 2018

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

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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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, Smith Bradley N, Marangi Giuseppe, Topp Simon D, Abramzon Yevgeniya, Gkazi Athina Soragia, Eicher John D, Kenna Aoife, ITALSGEN Consortium, 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, Genomic Translation for ALS Care (GTAC) Consortium, Moreno Cristiane de Araujo Martins, Kamalakaran Sitharthan, Goldstein David B, ALS Sequencing Consortium, Gitler Aaron D, Harris Tim, Myers Richard M, NYGC ALS Consortium, Phatnani Hemali, Musunuri Rajeeva Lochan, Evani Uday Shankar, Abhyankar Avinash, Zody Michael C, Answer ALS Foundation, 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, Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium, Benatar Michael, Taylor J Paul, Rampersaud Evadnie, Wu Gang, Wuu Joanne, SLAGEN Consortium, Lauria Giuseppe, Verde Federico, Fogh Isabella, Tiloca Cinzia, Comi Giacomo P, Sorarù Gianni, Cereda Cristina, French ALS Consortium, 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, Project MinE ALS Sequencing Consortium, 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

Аннотация

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.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты