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

ABSTRACT:

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 pho

SUBMITTER: Coku I 

PROVIDER: S-EPMC9543145 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature