LRRK2 mutation in familial Parkinson's disease in a Taiwanese population: Clinical, PET, and functional studies
Journal
Journal of Biomedical Science
Journal Volume
15
Journal Issue
5
Pages
661-667
Date Issued
2008
Author(s)
Abstract
Pathogenic mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal-dominant familial Parkinson's disease (PD). We performed clinical, imaging, and molecular functional studies in one family with the R1441H and six families with the G2385R variants of Lrrk2. To determine the contribution of these variants to familial PD in Taiwanese, we screened 32 Taiwanese or ethnic Chinese patients with familial PD for four pathogenic substitutions (R1441H, I2012T, I2020T, and G2019S) and one susceptibility polymorphism (G2385R). The frequencies of R1441H and G2385R were 3.7% and 22.2%, respectively. G2019S, I2012T, and I2020T were not detected. The clinical phenotypes and [ 18F]-dopa PET findings for subjects with R1441H or G2385R resembled those of patients with idiopathic PD; however, their lymphoblastoid cell lines showed increased apoptosis following exposure to a proteosome inhibitor. Thus, LRRK2 mutations are rare in Taiwanese with familial PD. Further study is needed to identify causative genes or unique biomarkers for familial PD. ? 2008 National Science Council.
SDGs
Other Subjects
DOPA; leucine rich repeat kinase 2; proteasome inhibitor; tioxamast; adult; aged; apoptosis; article; Chinese; clinical article; controlled study; female; gene frequency; gene mutation; genetic polymorphism; genetic screening; genetic susceptibility; genetic variability; human; human cell; lymphoblastoid cell line; male; Parkinson disease; pedigree analysis; phenotype; positron emission tomography; priority journal; protein function; Taiwan; Diagnostic Imaging; DNA Mutational Analysis; Family Health; Gene Frequency; Humans; Mutation, Missense; Parkinson Disease; Phenotype; Polymorphism, Genetic; Protein-Serine-Threonine Kinases; Taiwan
Type
journal article