The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 11 2022
12 11 2022
Historique:
received:
01
02
2022
accepted:
31
10
2022
entrez:
13
11
2022
pubmed:
14
11
2022
medline:
16
11
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36371497
doi: 10.1038/s41467-022-34620-y
pii: 10.1038/s41467-022-34620-y
pmc: PMC9653399
doi:
Substances chimiques
Superoxide Dismutase-1
EC 1.15.1.1
Superoxide Dismutase
EC 1.15.1.1
SOD1 protein, human
0
Types de publication
Observational Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6901Subventions
Organisme : NINDS NIH HHS
ID : R56 NS073873
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS073873
Pays : United States
Organisme : Medical Research Council
ID : MR/R024804/1
Pays : United Kingdom
Organisme : Motor Neurone Disease Association
ID : MCLAUGHLIN/OCT15/957-799
Pays : United Kingdom
Organisme : Motor Neurone Disease Association
ID : ALCHALABI-DOBSON/APR14/829-791
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
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