Détail du document
Identifiant
oai:HAL:hal-04122825v1
Sujet
[SDV.NEU]Life Sciences [q-bio]/Neu... [SDV.SPEE]Life Sciences [q-bio]/Sa...Auteur
Lanore, Aymeric Casse, Fanny Tesson, Christelle Courtin, Thomas Menon, Poornima Jayadev Sambin, S. Mangone, Graziella Mariani, L.-L. Lesage, S. Brice, Alexis Elbaz, Alexis Corvol, Jean ChristopheLangue
enEditeur
HAL CCSD;Wiley
Catégorie
CNRS - Centre national de la recherche scientifique
Année
2023
Date de référencement
15/12/2023
Mots clés
monogenic forms p = 0 disease lrrk2 mutations survival patients parkinsonRésumé
International audience; Objective: Survival of patients with monogenic Parkinson's disease may depend on the causative genes associated with the disease.
In this study, we compare survival of patients with Parkinson's disease according to the presence of SNCA, PRKN, LRRK2, or GBA mutations.Methods: Data from the French Parkinson Disease Genetics national multicenter cohort study were used.
Patients with sporadic and familial Parkinson's disease were recruited between 1990 and 2021.
Patients were genotyped for the presence of mutations in the SNCA, PRKN, LRRK2, or GBA genes.
Vital status was collected from the National death register for participants born in France.
Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using multivariable Cox proportional hazards regression.Results: Of the 2,037 patients with Parkinson's disease, 889 had died after a follow-up of up to 30 years.
Patients with PRKN (n = 100, HR = 0.41; p = 0.001) and LRRK2 mutations (n = 51, HR = 0.49; p = 0.023) had longer survival than those without any mutation, whereas patients with SNCA (n = 20, HR = 9.88; p < 0.001) or GBA mutations (n = 173, HR = 1.33; p = 0.048) had shorter survival.Interpretation: Survival differs across genetic forms of Parkinson's disease, with higher mortality for patients with SNCA or GBA mutations, and lower mortality for those with PRKN or LRRK2 mutations.
Differences in severity and disease progression among monogenic forms of Parkinson's disease likely explain these findings, which has important consequences for genetic counselling and choice of end points for future clinical trials for targeted therapies.
ANN NEUROL 2023.
Lanore, Aymeric,Casse, Fanny,Tesson, Christelle,Courtin, Thomas,Menon, Poornima Jayadev,Sambin, S.,Mangone, Graziella,Mariani, L.-L.,Lesage, S.,Brice, Alexis,Elbaz, Alexis,Corvol, Jean Christophe, 2023, Differences in Survival across Monogenic Forms of Parkinson's Disease, HAL CCSD;Wiley
Configurable Safety Tuning of Language Models with Synthetic Preference Data
data preference cst dpo configurable language safety
Affective flexibility as a developmental building block of cognitive reappraisal: An fMRI study
cognitive success affective flexibility
