Nature Communications (Nov 2022)
The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration
- Sarah Opie-Martin,
- Alfredo Iacoangeli,
- Simon D. Topp,
- Olubunmi Abel,
- Keith Mayl,
- Puja R. Mehta,
- Aleksey Shatunov,
- Isabella Fogh,
- Harry Bowles,
- Naomi Limbachiya,
- Thomas P. Spargo,
- Ahmad Al-Khleifat,
- Kelly L. Williams,
- Jennifer Jockel-Balsarotti,
- Taha Bali,
- Wade Self,
- Lyndal Henden,
- Garth A. Nicholson,
- Nicola Ticozzi,
- Diane McKenna-Yasek,
- Lu Tang,
- Pamela J. Shaw,
- Adriano Chio,
- Albert Ludolph,
- Jochen H. Weishaupt,
- John E. Landers,
- Jonathan D. Glass,
- Jesus S. Mora,
- Wim Robberecht,
- Philip Van Damme,
- Russell McLaughlin,
- Orla Hardiman,
- Leonard van den Berg,
- Jan H. Veldink,
- Phillippe Corcia,
- Zorica Stevic,
- Nailah Siddique,
- Vincenzo Silani,
- Ian P. Blair,
- Dong-sheng Fan,
- Florence Esselin,
- Elisa de la Cruz,
- William Camu,
- Nazli A. Basak,
- Teepu Siddique,
- Timothy Miller,
- Robert H. Brown,
- Ammar Al-Chalabi,
- Christopher E. Shaw
Affiliations
- Sarah Opie-Martin
- Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Alfredo Iacoangeli
- Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Simon D. Topp
- Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Olubunmi Abel
- Homerton University Hospital
- Keith Mayl
- Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Puja R. Mehta
- Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Aleksey Shatunov
- Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Isabella Fogh
- Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Harry Bowles
- Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Naomi Limbachiya
- Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Thomas P. Spargo
- Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Ahmad Al-Khleifat
- Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Kelly L. Williams
- Macquarie University Centre for MND Research, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University
- Jennifer Jockel-Balsarotti
- Department of Neurology, Washington University School of Medicine
- Taha Bali
- Department of Neurology, Washington University School of Medicine
- Wade Self
- Department of Neurology, Washington University School of Medicine
- Lyndal Henden
- Macquarie University Centre for MND Research, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University
- Garth A. Nicholson
- Macquarie University Centre for MND Research, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University
- Nicola Ticozzi
- Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano
- Diane McKenna-Yasek
- Department of Neurology, University of Massachusetts Medical School
- Lu Tang
- Department of Neurology, Peking University Third Hospital
- Pamela J. Shaw
- Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield
- Adriano Chio
- Rita Levi Montalcini’ Department of Neuroscience, University of Turin
- Albert Ludolph
- Department of Neurology, Ulm University
- Jochen H. Weishaupt
- Department of Neurology, University of Ulm
- John E. Landers
- Department of Neurology, University of Massachusetts Medical School
- Jonathan D. Glass
- Department Neurology, Emory University School of Medicine
- Jesus S. Mora
- ALS Unit, Department of Neurology, Hospital San Rafael
- Wim Robberecht
- Neurology Department, Univeristy Hospitals Leuven
- Philip Van Damme
- Neurology Department, Univeristy Hospitals Leuven
- Russell McLaughlin
- Complex Trait Genomics Laboratory, Smurfit Institute of Genetics, Trinity College Dublin
- Orla Hardiman
- Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin
- Leonard van den Berg
- Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht
- Jan H. Veldink
- Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht
- Phillippe Corcia
- Centre de Référence pour la SLA et les Autres Maladies du Motoneurone (FILSLAN)
- Zorica Stevic
- Neurology Clinic, Clinical Center of Serbia, School of Medicine, University of Belgrade
- Nailah Siddique
- Neuromuscular Disorders Program, Northwestern University, Feinberg School of Medicine
- Vincenzo Silani
- Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano
- Ian P. Blair
- Macquarie University Centre for MND Research, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University
- Dong-sheng Fan
- Department of Neurology, Peking University Third Hospital
- Florence Esselin
- Reference Center for ALS and Other Rare Motoneuron Disorders, University Hospital Gui de Chauliac
- Elisa de la Cruz
- Reference Center for ALS and Other Rare Motoneuron Disorders, University Hospital Gui de Chauliac
- William Camu
- Reference Center for ALS and Other Rare Motoneuron Disorders, University Hospital Gui de Chauliac
- Nazli A. Basak
- Koç University, School of Medicine Translational Medicine Research Center KUTTAM-NDAL
- Teepu Siddique
- Neuromuscular Disorders Program, Northwestern University, Feinberg School of Medicine
- Timothy Miller
- Department of Neurology, Washington University School of Medicine
- Robert H. Brown
- Department of Neurology, University of Massachusetts Medical School
- Ammar Al-Chalabi
- Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Christopher E. Shaw
- UK Dementia Research Institute Centre at King’s College London, School of Neuroscience, King’s College London
- DOI
- https://doi.org/10.1038/s41467-022-34620-y
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 9
Abstract
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.
