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The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration.
Opie-Martin, Sarah; Iacoangeli, Alfredo; Topp, Simon D; Abel, Olubunmi; Mayl, Keith; Mehta, Puja R; Shatunov, Aleksey; Fogh, Isabella; Bowles, Harry; Limbachiya, Naomi; Spargo, Thomas P; Al-Khleifat, Ahmad; Williams, Kelly L; Jockel-Balsarotti, Jennifer; Bali, Taha; Self, Wade; Henden, Lyndal; Nicholson, Garth A; Ticozzi, Nicola; McKenna-Yasek, Diane; Tang, Lu; Shaw, Pamela J; Chio, Adriano; Ludolph, Albert; Weishaupt, Jochen H; Landers, John E; Glass, Jonathan D; Mora, Jesus S; Robberecht, Wim; Damme, Philip Van; McLaughlin, Russell; Hardiman, Orla; van den Berg, Leonard; Veldink, Jan H; Corcia, Phillippe; Stevic, Zorica; Siddique, Nailah; Silani, Vincenzo; Blair, Ian P; Fan, Dong-Sheng; Esselin, Florence; de la Cruz, Elisa; Camu, William; Basak, Nazli A; Siddique, Teepu; Miller, Timothy; Brown, Robert H; Al-Chalabi, Ammar; Shaw, Christopher E.
Afiliação
  • Opie-Martin S; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9NU, UK.
  • Iacoangeli A; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9NU, UK.
  • Topp SD; Department of Biostatistics and Health Informatics, Institute of Psychiatry Psychology & Neuroscience, King's College London, SE5 8AF, London, UK.
  • Abel O; NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK.
  • Mayl K; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9NU, UK.
  • Mehta PR; Homerton University Hospital, Homerton Row, London, E9 6SR, UK.
  • Shatunov A; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9NU, UK.
  • Fogh I; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9NU, UK.
  • Bowles H; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9NU, UK.
  • Limbachiya N; Department of Molecular and Clinical Pharmacology, University of Liverpool, Blue Block 1.09, Sherrington Building, Crown St, Liverpool, L693BX, UK.
  • Spargo TP; Institute of Medicine, North-Eastern Federal University, 58 Belinsky str, Yakutsk, 677000, Russia.
  • Al-Khleifat A; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9NU, UK.
  • Williams KL; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9NU, UK.
  • Jockel-Balsarotti J; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9NU, UK.
  • Bali T; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9NU, UK.
  • Self W; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9NU, UK.
  • Henden L; Macquarie University Centre for MND Research, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.
  • Nicholson GA; Department of Neurology, Washington University School of Medicine, St Louis, MO, 63110, USA.
  • Ticozzi N; Department of Neurology, Washington University School of Medicine, St Louis, MO, 63110, USA.
  • McKenna-Yasek D; Department of Neurology, Washington University School of Medicine, St Louis, MO, 63110, USA.
  • Tang L; Macquarie University Centre for MND Research, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.
  • Shaw PJ; Macquarie University Centre for MND Research, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.
  • Chio A; Concord Clinical School, ANZAC Research Institute, Concord Repatriation Hospital, Sydney, NSW, 2139, Australia.
  • Ludolph A; Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, 20095, Cusano Milanino, MiIan, Italy.
  • Weishaupt JH; Dino Ferrari Center, Department of Pathophysiology and Transplantation, Center for Neurotechnology and Brain Therapeutics, Università degli Studi di Milano, Milan, Italy.
  • Landers JE; Department of Neurology, University of Massachusetts Medical School, Worcester, MA, 02125, USA.
  • Glass JD; Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, PR China.
  • Mora JS; Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, S10 2HQ, UK.
  • Robberecht W; Rita Levi Montalcini' Department of Neuroscience, University of Turin, Turin, Italy.
  • Damme PV; Neurology 1, AOU Città della Salute e della Scienza of Torino, Turin, 10124, Torino, Italy.
  • McLaughlin R; Department of Neurology, Ulm University, Oberer Eselsberg 45, 89081, Ulm, Germany.
  • Hardiman O; German Center for Neurodegenerative Diseases, DZNE, Ulm, Germany.
  • van den Berg L; Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081, Ulm, Germany.
  • Veldink JH; Division of Neurodegenerative Disorders, Department of Neurology, Mannheim Center for Translational Neuroscience, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
  • Corcia P; Department of Neurology, University of Massachusetts Medical School, Worcester, MA, 02125, USA.
  • Stevic Z; Department Neurology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
  • Siddique N; ALS Unit, Department of Neurology, Hospital San Rafael, 28016, Madrid, Spain.
  • Silani V; Neurology Department, Univeristy Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
  • Blair IP; Neurology Department, Univeristy Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
  • Fan DS; Neuroscience Department, KU Leuven and Center for Brain & Disease Research VIB Leuven, Leuven, Belgium.
  • Esselin F; Complex Trait Genomics Laboratory, Smurfit Institute of Genetics, Trinity College Dublin, Dublin, D02 PN40, Ireland.
  • de la Cruz E; Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, D02 PN40, Ireland.
  • Camu W; Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands.
  • Basak NA; Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands.
  • Siddique T; Centre de Référence pour la SLA et les Autres Maladies du Motoneurone (FILSLAN), 2 Avenue Martin Luther King, 87042, Limoges Cedex, France.
  • Miller T; Centre de Compétences Neuropathies Amyloïdes Familiales et Autres Neuropathies Périphériques Rares (NNERF), Poitiers, France.
  • Brown RH; Neurology Clinic, Clinical Center of Serbia, School of Medicine, University of Belgrade, Studentski trg 1, Belgrade, Serbia.
  • Al-Chalabi A; Neuromuscular Disorders Program, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60208, USA.
  • Shaw CE; Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, 20095, Cusano Milanino, MiIan, Italy.
Nat Commun ; 13(1): 6901, 2022 11 12.
Article em En | MEDLINE | ID: mdl-36371497
ABSTRACT
Superoxide dismutase (SOD1) gene variants may cause amyotrophic lateral sclerosis, some of which are associated with a distinct phenotype. Most studies assess limited variants or sample sizes. In this international, retrospective observational study, we compare phenotypic and demographic characteristics between people with SOD1-ALS and people with ALS and no recorded SOD1 variant. We investigate which variants are associated with age at symptom onset and time from onset to death or censoring using Cox proportional-hazards regression. The SOD1-ALS dataset reports age of onset for 1122 and disease duration for 883 people; the comparator population includes 10,214 and 9010 people respectively. Eight variants are associated with younger age of onset and distinct survival trajectories; a further eight associated with younger onset only and one with distinct survival only. Here we show that onset and survival are decoupled in SOD1-ALS. Future research should characterise rarer variants and molecular mechanisms causing the observed variability.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Esclerose Lateral Amiotrófica Tipo de estudo: Diagnostic_studies / Observational_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Esclerose Lateral Amiotrófica Tipo de estudo: Diagnostic_studies / Observational_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article