title: PINK1 mutation in Taiwanese early-onset parkinsonism : clinical, genetic, and dopamine transporter studies.
abstract: 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 (99m)Tc-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.
authors.affiliation: Neuroscience Research Center, Dept. of Neurology, Chang Gung Memorial Hospital and Chang Gung University, 33305, 5 Fu-Shin St., Kweishan, Taoyuan, Taiwan.
authors.forename: Yi-Hsin
authors.initials: YH
authors.lastname: Weng
authors.forename: Yah-Huei Wu
authors.initials: YH
authors.lastname: Chou
authors.forename: Wen-Shiang
authors.initials: WS
authors.lastname: Wu
authors.forename: Kun-Ju
authors.initials: KJ
authors.lastname: Lin
authors.forename: Hsiu-Chen
authors.initials: HC
authors.lastname: Chang
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
authors.forename: Rou-Shayn
authors.initials: RS
authors.lastname: Chen
authors.forename: Shiaw-Pyng
authors.initials: SP
authors.lastname: Wey
authors.forename: Chin-Song
authors.initials: CS
authors.lastname: Lu
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001931:Brain Mapping; D002648:Child; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D015609:Organotechnetium Compounds; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000235:genetics*; D010641:Phenotype; D011494:Protein Kinases / Q000235:genetics*; D013624:Taiwan; D015899:Tomography, Emission-Computed, Single-Photon; D014326:Tropanes; D000099202:PTEN-Induced Putative Kinase
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D015609:Organotechnetium Compounds; D011494:Protein Kinases; D014326:Tropanes; D000099202:PTEN-Induced Putative Kinase; C104196:technetium Tc 99m TRODAT-1