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首页> 外文期刊>Neuron >Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

机译：基因组 - 范围分析识别KIF5A作为新型ALS基因

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摘要

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.
机译：为了鉴定与ALS相关的新基因，我们进行了两种调查。我们进行了一种基因组 - 宽协会研究，比较了20,806 ALS病例和59,804个对照。独立地，我们进行了罕见的变体负荷分析，比较了1,138个指标家族ALS病例和19,494个控制。通过两种方法，我们将Kinesin家族成员5A（KIF5A）鉴定为与ALS相关的新基因。有趣的是，主要在KIF5a的N末端电机结构域中的突变是两个神经变性疾病的原因：遗传性痉挛截瘫（SPG10）和Charcot-Marie-tooth 2（CMT2）。相反，Als相关突变主要位于C末端性货舱结合尾部结构域，并且患有功能突变损失的患者相对于典型的ALS病例显示出延长的存活。总之，这些结果拓宽了kif5a中突变产生的表型光谱，并加强细胞骨骼缺陷在Als发病机制中的作用。

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  • 来源
    《Neuron》 |2018年第6期|共21页
  • 作者

    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; 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.; DAlfonso 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.; Soraru 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.; Luis Munoz-Blanco Jose; 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 Jesus 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-Perez Jesus; Garcia-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. Jr.; van den Berg Leonard H.; Veldink Jan H.; Harms Matthew B.; Glass Jonathan D.; Stone David J.; Tienari Pentti; Silani Vincenzo; Chio Adriano; Shaw Christopher E.; Traynor Bryan J.; Landers John E.;

  • 作者单位

    NIA Neuromuscular Dis Res Sect Lab Neurogenet NIH Porter Neurosci Res Ctr Bethesda MD 20892 USA;

    Univ Massachusetts Med Sch Dept Neurol Worcester MA 01605 USA;

    NIA Neuromuscular Dis Res Sect Lab Neurogenet NIH Porter Neurosci Res Ctr Bethesda MD 20892 USA;

    IRCCS Ist Auxol Italiano Dept Neurol Milan Italy;

    NIA Mol Genet Sect Lab Neurogenet NIH Porter Neurosci Res Ctr Bethesda MD 20892 USA;

    NIA Neuromuscular Dis Res Sect Lab Neurogenet NIH Porter Neurosci Res Ctr Bethesda MD 20892 USA;

    Univ Massachusetts Med Sch Dept Neurol Worcester MA 01605 USA;

    Univ Massachusetts Med Sch Dept Neurol Worcester MA 01605 USA;

    NIA Mol Genet Sect Lab Neurogenet NIH Porter Neurosci Res Ctr Bethesda MD 20892 USA;

    Univ Massachusetts Med Sch Dept Neurol Worcester MA 01605 USA;

    NIA Neuromuscular Dis Res Sect Lab Neurogenet NIH Porter Neurosci Res Ctr Bethesda MD 20892 USA;

    Univ Med Ctr Utrecht Brain Ctr Rudolf Magnus Dept Neurol Utrecht Netherlands;

    NIA Neuromuscular Dis Res Sect Lab Neurogenet NIH Porter Neurosci Res Ctr Bethesda MD 20892 USA;

    Univ Med Ctr Utrecht Brain Ctr Rudolf Magnus Dept Neurol Utrecht Netherlands;

    NINDS Neurodegenerat Dis Res Unit NIH Bethesda MD 20892 USA;

    Univ Med Ctr Utrecht Brain Ctr Rudolf Magnus Dept Neurol Utrecht Netherlands;

    NIA Neuromuscular Dis Res Sect Lab Neurogenet NIH Porter Neurosci Res Ctr Bethesda MD 20892 USA;

    Univ Massachusetts Med Sch Dept Neurol Worcester MA 01605 USA;

    Kings Coll London Maurice Wohl Clin Neurosci Inst Dept Basic &

    Clin Neurosci London SE5 9RS;

    NIA Neuromuscular Dis Res Sect Lab Neurogenet NIH Porter Neurosci Res Ctr Bethesda MD 20892 USA;

    Kings Coll London Maurice Wohl Clin Neurosci Inst Dept Basic &

    Clin Neurosci London SE5 9RS;

    NIA Neuromuscular Dis Res Sect Lab Neurogenet NIH Porter Neurosci Res Ctr Bethesda MD 20892 USA;

    Kings Coll London Maurice Wohl Clin Neurosci Inst Dept Basic &

    Clin Neurosci London SE5 9RS;

    Merck &

    Co Inc MRL Genet &

    Pharmacogenom Boston MA 02115 USA;

    Univ Massachusetts Med Sch Dept Neurol Worcester MA 01605 USA;

    IRCCS Salvatore Maugeri Fdn ALS Ctr Messina Italy;

    Univ Turin Rita Levi Montalcini Dept Neurosci Turin Italy;

    Maggiore della Carita Univ Hosp Novara Italy;

    Ist Sci San Raffaele Inst Expt Neurol Dept Neurol Div Neurosci Milan Italy;

    Azienda Osped Univ Modena St Agostino Estense Hosp Dept Neurosci Modena Italy;

    Osped Policlin San Martino Dept Neurosci Ophthalmol Genet Rehabil Materal &

    Genoa Italy;

    Univ Siena Dept Med Surg &

    Neurol Sci Siena Italy;

    IRCCS Salvatore Maugeri Fdn ALS Ctr Messina Italy;

    Univ Palermo ALS Clin Res Ctr Palermo Italy;

    CNR Inst Neurol Sci Cosenza Italy;

    Azienda Univ Osped Cagliari Dept Neurol Cagliari Italy;

    Univ Messina Dept Clin &

    Expt Med Messina Italy;

    Univ Bari Dept Basic Med Sci Neurosci &

    Sense Organs Bari Italy;

    Univ Campania Luigi Vanvitelli Dept Med Surg Neurol Metab &

    Aging Sci Naples Italy;

    IRCCS Ist Sci Neurol Bellaria Hosp Il Bene Ctr Immunol &

    Rare Neurol Dis Bologna Italy;

    Marche Polytech Univ Neurol Clin Ancona Italy;

    Univ Piemonte Orientale Dept Hlth Sci Novara Italy;

    Univ Piemonte Orientale Dept Hlth Sci Novara Italy;

    Univ G dAnnunzio Dept Neurol Chieti Italy;

    NIA Longitudinal Studies Sect Clin Res Branch NIH Baltimore MD 21224 USA;

    Columbia Univ Dept Neurol New York NY 10032 USA;

    Columbia Univ Inst Genom Med New York NY 10032 USA;

    Columbia Univ Inst Genom Med New York NY 10032 USA;

    Stanford Univ Sch Med Dept Genet Stanford CA 94305 USA;

    Bioverativ 225 2nd Ave Waltham MA 02145 USA;

    HudsonAlpha Inst Biotechnol Huntsville AL 35806 USA;

    New York Genome Ctr CGND New York NY USA;

    New York Genome Ctr Computat Biol New York NY USA;

    New York Genome Ctr Computat Biol New York NY USA;

    New York Genome Ctr Computat Biol New York NY USA;

    New York Genome Ctr Computat Biol New York NY USA;

    Gladstone Inst Neurol Dis San Francisco CA USA;

    Gladstone Inst Neurol Dis San Francisco CA USA;

    Gladstone Inst Neurol Dis San Francisco CA USA;

    MIT Dept Biol Engn 77 Massachusetts Ave Cambridge MA 02139 USA;

    Gladstone Inst Neurol Dis San Francisco CA USA;

    MIT Dept Biol Engn 77 Massachusetts Ave Cambridge MA 02139 USA;

    Cedars Sinai Med Ctr Board Governors Regenerat Med Inst Los Angeles CA 90048 USA;

    Univ Calif Irvine Inst Memory Impairment &

    Neurol Disorders Dept Neurobiol &

    Behav Irvine CA;

    Cedars Sinai Med Ctr Inst Heart Los Angeles CA USA;

    Harvard Med Sch Massachusetts Gen Hosp Dept Neurol Boston MA USA;

    Washington Univ Sch Med Dept Neurol St Louis MO 63110 USA;

    Ohio State Univ Wexner Med Ctr Dept Neurol Columbus OH 43210 USA;

    Harvard Med Sch Massachusetts Gen Hosp Dept Neurol Boston MA USA;

    Johns Hopkins Univ Dept Neurol Baltimore MD 21287 USA;

    Univ Miami Dept Neurol Miami FL 33136 USA;

    Howard Hughes Med Inst Chevy Chase MD 20815 USA;

    St Jude Childrens Res Hosp Dept Computat Biol Memphis TN 38105 USA;

    St Jude Childrens Res Hosp Dept Computat Biol Memphis TN 38105 USA;

    Univ Miami Dept Neurol Miami FL 33136 USA;

    Univ Milan Fdn IRCCS Ist Neurol Carlo Besta Motor Neuron Dis Ctr Neurol Unit 3 Milan Italy;

    IRCCS Ist Auxol Italiano Dept Neurol Milan Italy;

    IRCCS Ist Auxol Italiano Dept Neurol Milan Italy;

    IRCCS Ist Auxol Italiano Dept Neurol Milan Italy;

    IRCCS Fdn Ca Granda Osped Maggiore Policlin Neurol Unit Milan Italy;

    Univ Padua Dept Neurosci Padua Italy;

    IRCCS Mondino Fdn Genom &

    Postgenom Ctr Pavia Italy;

    Tours Univ CHU Bretonneau ALS Ctr Tours France;

    Univ Helsinki Helsinki Univ Hosp Dept Neurol FIN-02900 Helsinki Finland;

    Univ Helsinki Dept Pathol Helsinki Finland;

    Univ Helsinki Helsinki Univ Hosp Dept Neurol FIN-02900 Helsinki Finland;

    Univ Helsinki Helsinki Univ Hosp Dept Neurol FIN-02900 Helsinki Finland;

    Salford Royal NHS Fdn Trust Greater Manchester Neurosci Ctr Salford M6 8HD Lancs England;

    Salford Royal NHS Fdn Trust Greater Manchester Neurosci Ctr Salford M6 8HD Lancs England;

    Univ Manchester Fac Human &

    Med Sci Manchester M13 9PT Lancs England;

    Univ Manchester Fac Human &

    Med Sci Manchester M13 9PT Lancs England;

    UCL Inst Neurol Dept Clin Neurosci London NW3 2PG England;

    UCL Inst Neurol Dept Mol Neurosci Queen Sq House London WC1N 3BG England;

    Queen Mary Univ London NE London &

    Essex Reg Motor Neuron Dis Care Ctr Blizard Inst Ctr Neurosci;

    UCL Inst Neurol Dept Mol Neurosci Queen Sq House London WC1N 3BG England;

    NIA Mol Genet Sect Lab Neurogenet NIH Porter Neurosci Res Ctr Bethesda MD 20892 USA;

    NIA Neuromuscular Dis Res Sect Lab Neurogenet NIH Porter Neurosci Res Ctr Bethesda MD 20892 USA;

    NIA Genom Technol Grp Lab Neurogenet NIH Porter Neurosci Res Ctr Bethesda MD 20892 USA;

    Univ Massachusetts Med Sch Dept Neurol Worcester MA 01605 USA;

    Univ Massachusetts Med Sch Dept Neurol Worcester MA 01605 USA;

    Emory Univ Sch Med Dept Neurol Atlanta GA 30322 USA;

    Emory Univ Sch Med Dept Neurol Atlanta GA 30322 USA;

    Kings Coll London Maurice Wohl Clin Neurosci Inst Dept Basic &

    Clin Neurosci London SE5 9RS;

    Kings Coll London Maurice Wohl Clin Neurosci Inst Dept Basic &

    Clin Neurosci London SE5 9RS;

    Kings Coll London Maurice Wohl Clin Neurosci Inst Dept Basic &

    Clin Neurosci London SE5 9RS;

    Kings Coll London Maurice Wohl Clin Neurosci Inst Dept Basic &

    Clin Neurosci London SE5 9RS;

    Imperial Coll London Dept Med Div Brain Sci London W12 0NN England;

    Leiden Univ Med Ctr Dept Clin Genet Leiden Netherlands;

    Acad Med Ctr Dept Neurogenet &

    Neurol Amsterdam Netherlands;

    Hosp Gen Univ Gregorio Maranon IISGM ALS Neuromuscular Unit Madrid Spain;

    NIA Genom Technol Grp Lab Neurogenet NIH Porter Neurosci Res Ctr Bethesda MD 20892 USA;

    NIA Computat Biol Grp Lab Neurogenet NIH Porter Neurosci Res Ctr Bethesda MD 20892 USA;

    NIA Computat Biol Grp Lab Neurogenet NIH Porter Neurosci Res Ctr Bethesda MD 20892 USA;

    NINDS Neurodegenerat Dis Res Unit NIH Bethesda MD 20892 USA;

    NINDS Motor Neuron Disorders Unit NIH Bldg 36 Rm 4D04 Bethesda MD 20892 USA;

    Univ Illinois Dept Comp Sci Urbana IL USA;

    Univ Cattolica Sacro Cuore Ctr Geriatr Med Dept Geriatr Neurosci &

    Orthoped I-00168 Rome Italy;

    Barrow Neurol Inst Div Neurol Phoenix AZ 85013 USA;

    Univ Utah Sch Med Dept Neurol Salt Lake City UT USA;

    Univ Calif San Diego Dept Neurosci La Jolla CA 92093 USA;

    Mt Sinai Beth Israel Hosp Mt Sinai Sch Med New York NY USA;

    Univ Sheffield Sheffield Inst Translat Neurosci SITraN Sheffield S Yorkshire England;

    Cleveland Clin Neurol Inst Neuromuscular Ctr Dept Neurol Cleveland OH 44106 USA;

    Univ Sydney Brain &

    Mind Ctr Discipline Pathol 94 Mallett St Camperdown NSW 2050 Australia;

    Penn State Coll Med Dept Biochem Hershey PA USA;

    Penn State Coll Med Dept Pathol Hershey PA USA;

    Translat Genom Res Inst Neurogenom Div Phoenix AZ USA;

    Vet Affairs Boston Healthcare Syst Res &

    Dev Serv Boston MA USA;

    Boston Univ VA Boston Healthcare Syst Neurol Serv Boston MA 02130 USA;

    Johns Hopkins Univ Sch Med Dept Pathol Baltimore MD 21205 USA;

    UPMC Univ Paris 06 Sorbonne Univ Hop Pitie Salpetriere AP HP Inserm CNRS ICM Paris France;

    Univ Montpellier INM Montpellier France;

    Univ Montpellier INM Montpellier France;

    Drexel Univ Coll Med Dept Neurol Philadelphia PA 19104 USA;

    NIEHS Epidemiol Branch Durham NC 27709 USA;

    KU Leuven Univ Leuven Dept Neurosci Expt Neurol B-3000 Leuven Belgium;

    Cedars Sinai Med Ctr Dept Neurol Los Angeles CA 90048 USA;

    Tech Univ Munich Inst Human Genet Munich Germany;

    Tech Univ Munich Inst Human Genet Munich Germany;

    Kings Coll London Maurice Wohl Clin Neurosci Inst Dept Basic &

    Clin Neurosci London SE5 9RS;

    Univ Med Ctr Utrecht Brain Ctr Rudolf Magnus Dept Neurol Utrecht Netherlands;

    Univ Lisbon Fac Med Inst Mol Med Inst Physiol Lisbon Portugal;

    SURFsara Amsterdam Netherlands;

    Univ Med Ctr Utrecht Brain Ctr Rudolf Magnus Dept Neurol Utrecht Netherlands;

    KU Leuven Univ Leuven Dept Neurosci Expt Neurol B-3000 Leuven Belgium;

    Trin Coll Dublin Smurfit Inst Genet Populat Genet Lab Dublin Ireland;

    Univ Med Ctr Utrecht Brain Ctr Rudolf Magnus Dept Neurol Utrecht Netherlands;

    Kantonsspital St Gallen ALS Clin Neuromuscular Dis Ctr St Gallen Switzerland;

    Mayo Clin Florida Dept Neurol Jacksonville FL 32224 USA;

    Mayo Clin Dept Neurosci Jacksonville FL 32224 USA;

    Mayo Clin Dept Neurosci Jacksonville FL 32224 USA;

    Univ Southampton Fac Med Southampton Hants England;

    Bogazici Univ Suna &

    Inan Kirac Fdn Neurodegenerat Res Lab Istanbul Turkey;

    Hosp San Rafael ALS Unit Neurol Madrid Spain;

    Tel Aviv Sourasky Med Ctr Dept Neurol Tel Aviv Israel;

    Univ Sheffield Sheffield Inst Translat Neurosci SITraN Sheffield S Yorkshire England;

    Univ Oxford Nuffield Dept Clin Neurosci Oxford England;

    Univ Oxford Nuffield Dept Clin Neurosci Oxford England;

    Trinity Coll Dublin Trinity Biomed Sci Inst Acad Unit Neurol Dublin Ireland;

    Macquarie Univ Fac Med &

    Hlth Sci Ctr MND Res Sydney NSW 2109 Australia;

    Macquarie Univ Fac Med &

    Hlth Sci Ctr MND Res Sydney NSW 2109 Australia;

    Macquarie Univ Fac Med &

    Hlth Sci Ctr MND Res Sydney NSW 2109 Australia;

    Macquarie Univ Fac Med &

    Hlth Sci Ctr MND Res Sydney NSW 2109 Australia;

    McGill Univ Dept Neurol &

    Neurosurg Montreal Neurol Inst Montreal PQ Canada;

    Hosp 12 Octubre Madrid SERMAS Inst Invest Unidad ELA Madrid Spain;

    Hosp 12 Octubre Madrid SERMAS Inst Invest Unidad ELA Madrid Spain;

    Kings Coll London Maurice Wohl Clin Neurosci Inst Dept Basic &

    Clin Neurosci London SE5 9RS;

    Univ Toronto Dept Med Div Neurol Tanz Ctr Res Neurodegenerat Dis Toronto ON M5S 3H2 Canada;

    Univ Toronto Sunnybrook Hlth Sci Ctr Dept Internal Med Div Neurol Toronto ON M4N 3M5 Canada;

    Johns Hopkins Univ Dept Neurol Baltimore MD 21287 USA;

    Johns Hopkins Univ Dept Neurol Baltimore MD 21287 USA;

    Johns Hopkins Univ Dept Neurol Baltimore MD 21287 USA;

    Penn State Hershey Med Ctr Dept Neurol Hershey PA USA;

    Univ Sheffield Sheffield Inst Translat Neurosci SITraN Sheffield S Yorkshire England;

    UPMC Univ Paris 06 Sorbonne Univ Hop Pitie Salpetriere AP HP Inserm CNRS ICM Paris France;

    Univ Michigan Dept Neurol Ann Arbor MI USA;

    Univ Michigan Dept Neurol Ann Arbor MI USA;

    Univ Utah Sch Med Dept Neurol Salt Lake City UT USA;

    Fondazione IRCCS Ist Neurol Carlo Besta Unit Genet Neurodegenerat &

    Metab Dis I-20133 Milan Italy;

    IRCCS Ist Auxol Italiano Dept Neurol Milan Italy;

    Fondazione IRCCS Ist Neurol Carlo Besta Unit Genet Neurodegenerat &

    Metab Dis I-20133 Milan Italy;

    KU Leuven Univ Leuven Dept Neurosci Expt Neurol B-3000 Leuven Belgium;

    KU Leuven Univ Leuven Dept Neurosci Expt Neurol B-3000 Leuven Belgium;

    UCL Inst Neurol Sobell Dept Motor Neurosci &

    Movement Disor London England;

    Catholic Univ Inst Neurol Ctr Clini NeMO Largo F Vito 1 I-00168 Rome Italy;

    Serena Onlus Fdn NEuroMuscular Omnictr NEMO Milan Italy;

    Ulm Univ Neurol Dept Albert Einstein Allee 11 D-89081 Ulm Germany;

    Umea Univ Dept Pharmacol &

    Clin Neurosci SE-90185 Umea Sweden;

    Ulm Univ Neurol Dept Albert Einstein Allee 11 D-89081 Ulm Germany;

    Univ Montpellier CHU Gui de Chauliac ALS Ctr Montpellier France;

    Univ Penn Dept Pathol &

    Lab Med Philadelphia PA USA;

    Univ Penn Dept Pathol &

    Lab Med Philadelphia PA USA;

    Univ Massachusetts Med Sch Dept Neurol Worcester MA 01605 USA;

    Univ Med Ctr Utrecht Brain Ctr Rudolf Magnus Dept Neurol Utrecht Netherlands;

    Univ Med Ctr Utrecht Brain Ctr Rudolf Magnus Dept Neurol Utrecht Netherlands;

    Columbia Univ Dept Neurol New York NY 10032 USA;

    Emory Univ Sch Med Dept Neurol Atlanta GA 30322 USA;

    Merck &

    Co Inc MRL Genet &

    Pharmacogen West Point PA 19486 USA;

    Univ Helsinki Helsinki Univ Hosp Dept Neurol FIN-02900 Helsinki Finland;

    IRCCS Ist Auxol Italiano Dept Neurol Milan Italy;

    Univ Turin Rita Levi Montalcini Dept Neurosci Turin Italy;

    Kings Coll London Maurice Wohl Clin Neurosci Inst Dept Basic &

    Clin Neurosci London SE5 9RS;

    NIA Neuromuscular Dis Res Sect Lab Neurogenet NIH Porter Neurosci Res Ctr Bethesda MD 20892 USA;

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