ORIGINAL COMMUNICATION

Journal of Neurology

, Volume 254, Issue 10, pp 1347-1355

PINK1 mutation in Taiwanese early-onset parkinsonism

Clinical, genetic, and dopamine transporter studies
  • Yi-Hsin WengAffiliated withNeuroscience Research Center, Section of Movement Disorders, Dept. of Neurology, Chang Gung Memorial Hospital and Chang Gung UniversityNeuroscience Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine
  • , Yah-Huei Wu ChouAffiliated withHuman Molecular Genetic Laboratory, Chang Gung Memorial Hospital Chang Gung University College of MedicineNeuroscience Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine
  • , Wen-Shiang WuAffiliated withNeuroscience Research Center, Section of Movement Disorders, Dept. of Neurology, Chang Gung Memorial Hospital and Chang Gung University
  • , Kun-Ju LinAffiliated withDept. of Nuclear Medicine, Chang Gung Memorial Hospital Chang Gung University College of MedicineNeuroscience Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine
  • , Hsiu-Chen ChangAffiliated withNeuroscience Research Center, Section of Movement Disorders, Dept. of Neurology, Chang Gung Memorial Hospital and Chang Gung University
  • , Tzu-Chen YenAffiliated withDept. of Nuclear Medicine, Chang Gung Memorial Hospital Chang Gung University College of MedicineNeuroscience Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine
  • , Rou-Shayn ChenAffiliated withNeuroscience Research Center, Section of Movement Disorders, Dept. of Neurology, Chang Gung Memorial Hospital and Chang Gung UniversityNeuroscience Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine
  • , Shiaw-Pyng WeyAffiliated withDept. of Medical Imaging and Radiological Sciences, Chang Gung Memorial Hospital Chang Gung University College of Medicine
  • , Chin-Song LuAffiliated withNeuroscience Research Center, Section of Movement Disorders, Dept. of Neurology, Chang Gung Memorial Hospital and Chang Gung UniversityNeuroscience Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine Email author 

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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 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.

Key words

PINK1 gene early-onset Parkinson's disease dopamine transporter 99mTc-TRODAT-1 SPECT