| Summary: | 碩士 === 國立臺灣師範大學 === 生命科學研究所 === 96 === Abstract
Parkinson’s disease (PD), the second most common neurodegenerative disorder, is characterized by resting tremor, rigidity, bradykinesia, and postural instability. The symptoms of PD in pathology are neuronal loss in the basal ganglia, especially in the substantia nigra pars compacta, and presence of intracellular Lewy body inclusions in surviving neurons. Mutations in leucine-rich repeat kinase 2 (LRRK2, encoding dardarin) are the most frequent genetic cause of PD known nowadays. Mutations in different functional regions of LRRK2 have been reported. Studies from China, Singapore, and Japan indicate that the G2385R polymorphism is an ancient and common risk factor for sporadic PD in the Asian population. In this study, we screened LRRK2 mutations in PD patients and identified a reported (R1441H) and two novel (R767H and S885N) mutations, in addition to 5 nonsynonymous and 8 synonymous amino acid substitutions. In the case-control study, the frequency of the heterozygous G2385R genotype was higher in PD compared to controls (8.4 vs. 4.2%, odds ratio = 2.08, 95% CI: 1.05-4.41, P = 0.044). Moreover, M2397T acting synergistically with G2385R to play role in PD susceptibility (4.2 vs. 0.4%, odds ratio = 10.63, 95% CI: 2.08-194.26, P = 0.024). Granulin (GRN) has been identified as one of the gene responsible for frontotemporal dementia (FTD) and mutations in GRN have been reported. Using cDNA sequencing, we found two novel mutations L57M and T487I, additionally to a synonymous D128 and a C>T variation in 3’UTR. The studies may provide a tool for clinical diagnosis and counseling.
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