Functional Analyses of Two Novel LRRK2 Pathogenic Variants in Familial Parkinson's Disease. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Movement Disorders Année : 2022

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

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Ilda Coku
  • Fonction : Auteur
Claire Deldycke
  • Fonction : Auteur
Guillaume Baille
  • Fonction : Auteur
Gaëlle Vermeersch
  • Fonction : Auteur
Luc Buée

Résumé

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.

Dates et versions

hal-03703786 , version 1 (24-06-2022)

Identifiants

Citer

Ilda Coku, Eugénie Mutez, Sabiha Eddarkaoui, Sébastien Carrier, Antoine Marchand, et al.. Functional Analyses of Two Novel LRRK2 Pathogenic Variants in Familial Parkinson's Disease.. Movement Disorders, 2022, ⟨10.1002/mds.29124⟩. ⟨hal-03703786⟩
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