The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration.

Autor: 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.; Department of Biostatistics and Health Informatics, Institute of Psychiatry Psychology & Neuroscience, King's College London, SE5 8AF, London, UK.; NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK., Topp SD; 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., Abel O; Homerton University Hospital, Homerton Row, London, E9 6SR, 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; 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., 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.; Department of Molecular and Clinical Pharmacology, University of Liverpool, Blue Block 1.09, Sherrington Building, Crown St, Liverpool, L693BX, UK.; Institute of Medicine, North-Eastern Federal University, 58 Belinsky str, Yakutsk, 677000, Russia., 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 Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9NU, UK., Spargo TP; 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., 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; Macquarie University Centre for MND Research, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia., Jockel-Balsarotti J; Department of Neurology, Washington University School of Medicine, St Louis, MO, 63110, USA., Bali T; Department of Neurology, Washington University School of Medicine, St Louis, MO, 63110, USA., Self W; Department of Neurology, Washington University School of Medicine, St Louis, MO, 63110, USA., 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; Macquarie University Centre for MND Research, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.; Concord Clinical School, ANZAC Research Institute, Concord Repatriation Hospital, Sydney, NSW, 2139, Australia., Ticozzi N; Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, 20095, Cusano Milanino, MiIan, Italy.; Dino Ferrari Center, Department of Pathophysiology and Transplantation, Center for Neurotechnology and Brain Therapeutics, Università degli Studi di Milano, Milan, Italy., McKenna-Yasek D; Department of Neurology, University of Massachusetts Medical School, Worcester, MA, 02125, USA., Tang L; Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, PR China., Shaw PJ; Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, S10 2HQ, UK., Chio A; Rita Levi Montalcini' Department of Neuroscience, University of Turin, Turin, Italy.; Neurology 1, AOU Città della Salute e della Scienza of Torino, Turin, 10124, Torino, Italy., Ludolph A; Department of Neurology, Ulm University, Oberer Eselsberg 45, 89081, Ulm, Germany.; German Center for Neurodegenerative Diseases, DZNE, Ulm, Germany., Weishaupt JH; Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081, Ulm, Germany.; Division of Neurodegenerative Disorders, Department of Neurology, Mannheim Center for Translational Neuroscience, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany., Landers JE; Department of Neurology, University of Massachusetts Medical School, Worcester, MA, 02125, USA., Glass JD; Department Neurology, Emory University School of Medicine, Atlanta, GA, 30322, USA., Mora JS; ALS Unit, Department of Neurology, Hospital San Rafael, 28016, Madrid, Spain., Robberecht W; Neurology Department, Univeristy Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium., Damme PV; Neurology Department, Univeristy Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.; Neuroscience Department, KU Leuven and Center for Brain & Disease Research VIB Leuven, Leuven, Belgium., McLaughlin R; Complex Trait Genomics Laboratory, Smurfit Institute of Genetics, Trinity College Dublin, Dublin, D02 PN40, Ireland., Hardiman O; Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, D02 PN40, Ireland., van den Berg L; Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands., Veldink JH; Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands., Corcia P; Centre de Référence pour la SLA et les Autres Maladies du Motoneurone (FILSLAN), 2 Avenue Martin Luther King, 87042, Limoges Cedex, France.; Centre de Compétences Neuropathies Amyloïdes Familiales et Autres Neuropathies Périphériques Rares (NNERF), Poitiers, France., Stevic Z; Neurology Clinic, Clinical Center of Serbia, School of Medicine, University of Belgrade, Studentski trg 1, Belgrade, Serbia., Siddique N; Neuromuscular Disorders Program, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60208, USA., Silani V; Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, 20095, Cusano Milanino, MiIan, Italy.; Dino Ferrari Center, Department of Pathophysiology and Transplantation, Center for Neurotechnology and Brain Therapeutics, Università degli Studi di Milano, Milan, Italy., Blair IP; Macquarie University Centre for MND Research, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia., Fan DS; Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, PR China., Esselin F; Reference Center for ALS and Other Rare Motoneuron Disorders, University Hospital Gui de Chauliac, 34295, Montpellier, France., de la Cruz E; Reference Center for ALS and Other Rare Motoneuron Disorders, University Hospital Gui de Chauliac, 34295, Montpellier, France., Camu W; Reference Center for ALS and Other Rare Motoneuron Disorders, University Hospital Gui de Chauliac, 34295, Montpellier, France., Basak NA; Koç University, School of Medicine Translational Medicine Research Center KUTTAM-NDAL, 34450, Sarıyer, Istanbul, Turkey., Siddique T; Neuromuscular Disorders Program, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60208, USA., Miller T; Department of Neurology, Washington University School of Medicine, St Louis, MO, 63110, USA., Brown RH; Department of Neurology, University of Massachusetts Medical School, Worcester, MA, 02125, USA., Al-Chalabi 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., Shaw CE; UK Dementia Research Institute Centre at King's College London, School of Neuroscience, King's College London, Strand, London, WC2R 2LS, UK. chris.shaw@kcl.ac.uk.; Centre for Brain Research, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand. chris.shaw@kcl.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Nov 12; Vol. 13 (1), pp. 6901. Date of Electronic Publication: 2022 Nov 12.
DOI: 10.1038/s41467-022-34620-y
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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