Predictors for progression in amyotrophic lateral sclerosis associated to SOD1 mutation: insight from two population-based registries.
ALS
Amyotrophic lateral sclerosis
Genotype–phenotype
Population-based register
Prognostic factors
SOD1
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
07
06
2023
accepted:
21
08
2023
revised:
19
08
2023
medline:
9
11
2023
pubmed:
5
9
2023
entrez:
5
9
2023
Statut:
ppublish
Résumé
Uncovering distinct features and trajectories of amyotrophic lateral sclerosis (ALS) associated with SOD1 mutations (SOD1-ALS) can provide valuable insights for patient' counseling and stratification for trials, and interventions timing. Our study aims to pinpoint distinct clinical characteristics of SOD1-ALS by delving into genotype-phenotype correlations and factors that potentially impact disease progression. This is a retrospective observational study of a SOD1-ALS cohort from two Italian registers situated in the regions of Emilia-Romagna, Piedmont and Valle d'Aosta. Out of 2204 genotyped ALS patients, 2.5% carried SOD1 mutations, with a M:F ratio of 0.83. SOD1-ALS patients were younger, and more frequently reported a family history of ALS and/or FTD. SOD1-ALS had a longer survival compared to patients without ALS-associated gene mutations. However, here was considerable variability in survival across distinct SOD1 mutations, with an average survival of less than a year for the L39V, G42S, G73S, D91N mutations. Among SOD1-ALS, multivariate analysis showed that, alongside established clinical prognostic factors such as advanced age at onset and high progression rate at diagnosis, mutations located in exon 2 or within highly conserved gene positions predicted worse survival. Conversely, among comorbidities, cancer history was independently associated with longer survival. Within the context of an overall slower disease, SOD1-ALS exhibits some degree of heterogeneity linked to the considerable genetic diversity arising from the multitude of potential mutations sites and specific clinical prognostic factors, including cancer history. Revealing the factors that modulate the phenotypic heterogeneity of SOD1-ALS could prove advantageous in improving the efficacy of upcoming therapeutic approaches.
Sections du résumé
BACKGROUND
BACKGROUND
Uncovering distinct features and trajectories of amyotrophic lateral sclerosis (ALS) associated with SOD1 mutations (SOD1-ALS) can provide valuable insights for patient' counseling and stratification for trials, and interventions timing. Our study aims to pinpoint distinct clinical characteristics of SOD1-ALS by delving into genotype-phenotype correlations and factors that potentially impact disease progression.
METHODS
METHODS
This is a retrospective observational study of a SOD1-ALS cohort from two Italian registers situated in the regions of Emilia-Romagna, Piedmont and Valle d'Aosta.
RESULTS
RESULTS
Out of 2204 genotyped ALS patients, 2.5% carried SOD1 mutations, with a M:F ratio of 0.83. SOD1-ALS patients were younger, and more frequently reported a family history of ALS and/or FTD. SOD1-ALS had a longer survival compared to patients without ALS-associated gene mutations. However, here was considerable variability in survival across distinct SOD1 mutations, with an average survival of less than a year for the L39V, G42S, G73S, D91N mutations. Among SOD1-ALS, multivariate analysis showed that, alongside established clinical prognostic factors such as advanced age at onset and high progression rate at diagnosis, mutations located in exon 2 or within highly conserved gene positions predicted worse survival. Conversely, among comorbidities, cancer history was independently associated with longer survival.
INTERPRETATION
CONCLUSIONS
Within the context of an overall slower disease, SOD1-ALS exhibits some degree of heterogeneity linked to the considerable genetic diversity arising from the multitude of potential mutations sites and specific clinical prognostic factors, including cancer history. Revealing the factors that modulate the phenotypic heterogeneity of SOD1-ALS could prove advantageous in improving the efficacy of upcoming therapeutic approaches.
Identifiants
pubmed: 37668704
doi: 10.1007/s00415-023-11963-0
pii: 10.1007/s00415-023-11963-0
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
Langues
eng
Sous-ensembles de citation
IM
Pagination
6081-6092Subventions
Organisme : Ministero della Salute
ID : RF-2016-02362405
Organisme : Seventh Framework Programme
ID : 259867
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : 2017SNW5MB
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : 101017598
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.
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