Differences in Survival across Monogenic Forms of Parkinson's Disease.

Autor: Lanore A; Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, Paris, France.; Assistance Publique Hôpitaux de Paris, Department of Neurology, CIC Neurosciences, Hôpital Pitié-Salpêtrière, Paris, France., Casse F; Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, Paris, France., Tesson C; Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, Paris, France., Courtin T; Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, Paris, France.; Assistance Publique Hôpitaux de Paris, Department of Genetics, Hôpital Pitié-Salpêtrière, Paris, France., Menon PJ; Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, Paris, France.; Assistance Publique Hôpitaux de Paris, Department of Neurology, CIC Neurosciences, Hôpital Pitié-Salpêtrière, Paris, France.; School of Postgraduate Studies, Royal College of Surgeons in Ireland, Dublin, Ireland., Sambin S; Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, Paris, France.; Assistance Publique Hôpitaux de Paris, Department of Neurology, CIC Neurosciences, Hôpital Pitié-Salpêtrière, Paris, France., Mangone G; Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, Paris, France.; Assistance Publique Hôpitaux de Paris, Department of Neurology, CIC Neurosciences, Hôpital Pitié-Salpêtrière, Paris, France.; Department of Neurology, Movement Disorder Division, Rush University Medical Center, Chicago, IL., Mariani LL; Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, Paris, France.; Assistance Publique Hôpitaux de Paris, Department of Neurology, CIC Neurosciences, Hôpital Pitié-Salpêtrière, Paris, France., Lesage S; Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, Paris, France., Brice A; Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, Paris, France.; Assistance Publique Hôpitaux de Paris, Department of Genetics, Hôpital Pitié-Salpêtrière, Paris, France., Elbaz A; Université Paris-Saclay, UVSQ, Univ. Paris-Sud, Inserm, Équipe 'Exposome, heredity, Cancer, and Health', CESP, Villejuif, France., Corvol JC; Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, Paris, France.; Assistance Publique Hôpitaux de Paris, Department of Neurology, CIC Neurosciences, Hôpital Pitié-Salpêtrière, Paris, France.
Jazyk: angličtina
Zdroj: Annals of neurology [Ann Neurol] 2023 Jul; Vol. 94 (1), pp. 123-132. Date of Electronic Publication: 2023 Mar 27.
DOI: 10.1002/ana.26636
Abstrakt: 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;94:123-132.
(© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
Databáze: MEDLINE
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