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The PINK1 gene mutation is probably the second most common genetic cause of early-onset Parkinson's disease (EOPD). The frequency and the characteristics of the PINK1 mutation in the Taiwanese population are unknown. This study was designed to investigate the genotype, phenotype and dopaminergic function of PINK1 in a cohort of EOPD patients. The genetic settings were to detect the PINK1 gene mutations in 138 EOPD patients and in 191 controls. Using the 99mTc-TRODAT-1 (TRODAT) scan, we investigated the differences in the dopamine transporter (DAT) activities between the PINK1 patients, late-onset Parkinson's disease (LOPD) patients and healthy controls. Four EOPD patients with 3 genotypic mutations in the PINK1 gene were found: a compound heterozygous mutation (Q239X/R492X) in 2 sisters, a novel homozygous mutation (R492X) in a woman, and a novel heterozygous mutation (G193R) in a man. The three PINK1 patients had typical phenotype with juvenile onset, benign course, and frequently with dyskinesias. The TRODAT scan showed a rather even and symmetrical reduction of uptake in PINK1 patients, unlike the dominant decline in the putamen in the LOPD patients. The annual reduction rate of uptake in the striatum was much slower in PINK1 patients than that in the LOPD patients (1.7 % vs. 4.1%; p<0.005). In the patient with a heterozygous mutation in the PINK1 gene, the reduction ratio in the striatum, as well as the annual reduction rate, were closer to those in the LOPD group. We conclude that the incidence of carrying PINK1 mutations in the present cohort of Taiwanese EOPD patients was low, accounting for 2/39 (5.1 %) in familial cases, and 2/99 (2 %) in sporadic cases. The slower annual reduction of DAT activity might indicate the insidious degeneration of dopamine neurons and a benign prognosis. [ABSTRACT FROM AUTHOR]

Nigral dopaminergic projections to the striatum are targeted in Parkinson’s disease (PD). The extent of the degeneration of the dopaminergic system in PD can be visualised by dopamine transporter imaging using single-photon emission tomography (SPET). In this study in 188 patients with PD, we analysed the image patterns and compared them with the clinical features in order to verify the usefulness of technetium-99m TRODAT-1 brain SPET in the evaluation of patients with PD. Two independent readers visually assessed SPET slices from three brain axes according to a “fine” visual scale; results were also grouped according to a “rough” visual scale. Results of both visual and semi-quantitative analyses were compared among patients with different stages of PD and healthy controls. There was good agreement between the readers in the interpretation of the image patterns [kappa statistic (κ)=0.85 for the presence of PD; κ=0.88 for the rough scale and 0.81 for the fine scale]. Good concordance was obtained when visual interpretation was used to evaluate the presence of PD (sensitivity =98%, specificity =86%, κ=0.85). Semi-quantitative analyses revealed significant negative correlations between both striatal and putaminal uptake and disease severity as assessed using the Hoehn and Yahr scale (ρ=-0.89 and -0.93 respectively). An apparent decrease in striatal uptake in early PD, hardly discernible from the uptake level in advanced PD, was commonly found in visual analyses. The results suggest that both visual and semi-quantitative analyses of [sup 99m]Tc-TRODAT-1 SPET images reflect neurodegeneration in PD, and that [sup 99m]Tc-TRODAT-1 SPET represents an adequate means for evaluation of the status of patients with PD. [ABSTRACT FROM AUTHOR]