Title :

Functional Analyses of Two Novel LRRK2 Pathogenic Variants in Familial Parkinson's Disease.

Author(s) :

Coku, Ilda [Auteur]
Mutez, Eugénie [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Eddarkaoui, Sabiha [Auteur]
Excellence Laboratory LabEx DISTALZ
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Carrier, Sébastien [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Marchand, Antoine [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Deldycke, Claire [Auteur]
Goveas, Liesel [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Baille, Guillaume [Auteur]
Tir, Mélissa [Auteur]
Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 [LNFP]
Magnez, Romain [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Thuru, Xavier [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Vermeersch, Gaëlle [Auteur]
Vandenberghe, Wim [Auteur]
Department of Information Technology [INTEC]
Buee, Luc [Auteur]
Equipe Alzheimer and Tauopathies - LilNCog [U1172 Inserm]
DEFEBVRE, Luc [Auteur]
Département de neurologie [Lille]
Sablonnière, Bernard [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Chartier-Harlin, Marie-Christine [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Taymans, Jean-Marc [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Huin, Vincent [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]

Journal title :

MOVEMENT DISORDERS

Publisher :

Wiley

Publication date :

2022

ISSN :

0885-3185

HAL domain(s) :

Sciences du Vivant [q-bio]/Médecine humaine et pathologie

English abstract : [en]

BACKGROUND: Pathogenic variants in the LRRK2 gene are a common monogenic cause of Parkinson's disease. However, only seven variants have been confirmed to be pathogenic. OBJECTIVES: We identified two novel LRRK2 variants ...
Show more >BACKGROUND: Pathogenic variants in the LRRK2 gene are a common monogenic cause of Parkinson's disease. However, only seven variants have been confirmed to be pathogenic. OBJECTIVES: We identified two novel LRRK2 variants (H230R and A1440P) and performed functional testing. METHODS: We transiently expressed wild-type, the two new variants, or two known pathogenic mutants (G2019S and R1441G) in HEK-293\,T cells, with or without LRRK2 kinase inhibitor treatment. We characterized the phosphorylation and kinase activity of the mutants by western blotting. Thermal shift assays were performed to determine the folding and stability of the LRRK2 proteins. RESULTS: The two variants were found in two large families and segregate with the disease. They display altered LRRK2 phosphorylation and kinase activity. CONCLUSIONS: We identified two novel LRRK2 variants which segregate with the disease. The results of functional testing lead us to propose these two variants as novel causative mutations for familial Parkinson's disease. \textcopyright 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL