LRRK2 mutation in familial Parkinson's disease in a Taiwanese population: clinical, PET, and functional studies.
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 [(18)F]-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.
Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei 100, Taiwan.
Chin-Hsien
CH
Lin
Kai-Yuan
KY
Tzen
Chin-Yi
CY
Yu
Chun-Hwei
CH
Tai
Matthew J
MJ
Farrer
Ruey-Meei
RM
Wu
D004252:DNA Mutational Analysis; D003952:Diagnostic Imaging; D005192:Family Health; D005787:Gene Frequency; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D020125:Mutation, Missense; D010300:Parkinson Disease / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013624:Taiwan
C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases