{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Coku I"],"funding":["Centre Hospitalier Régional Universitaire de Montpellier","Association France Parkinson","Agence Nationale de la Recherche","Association France Alzheimer","Fondation de France","Institut National de la Santé et de la Recherche Médicale","DISTALZ","Michael J. Fox Foundation for Parkinson&apos;s Research"],"pagination":["1761-1767"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9543145"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["37(8)"],"pubmed_abstract":["<h4>Background</h4>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.<h4>Objectives</h4>We identified two novel LRRK2 variants (H230R and A1440P) and performed functional testing.<h4>Methods</h4>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.<h4>Results</h4>The two variants were found in two large families and segregate with the disease. They display altered LRRK2 pho"],"journal":["Movement disorders : official journal of the Movement Disorder Society"],"pubmed_title":["Functional Analyses of Two Novel LRRK2 Pathogenic Variants in Familial Parkinson's Disease."],"pmcid":["PMC9543145"],"funding_grant_id":["Maladie de Parkinson","10255.03","ANR‐21‐CE16‐0003‐01 PARK‐PEP","R16008","12938.04","ANR‐16‐CE16‐0012‐02 MeTDePaDi","ANR‐20‐CE16‐0008 Synapark","6709.03","R19199EK"],"pubmed_authors":["Vermeersch G","Buee L","Marchand A","Eddarkaoui S","Carrier S","Defebvre L","Deldycke C","Chartier-Harlin MC","Goveas L","Magnez R","Thuru X","Vandenberghe W","Sablonniere B","Huin V","Baille G","Tir M","Taymans JM","Coku I","Mutez E"],"additional_accession":[]},"is_claimable":false,"name":"Functional Analyses of Two Novel LRRK2 Pathogenic Variants in Familial Parkinson's Disease.","description":"<h4>Background</h4>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.<h4>Objectives</h4>We identified two novel LRRK2 variants (H230R and A1440P) and performed functional testing.<h4>Methods</h4>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.<h4>Results</h4>The two variants were found in two large families and segregate with the disease. They display altered LRRK2 pho","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Aug","modification":"2026-07-14T15:50:20.519Z","creation":"2025-04-06T00:15:18.471Z"},"accession":"S-EPMC9543145","cross_references":{"pubmed":["35708213"],"doi":["10.1002/mds.29124"]}}