Journal of Neurology

, 254:1347

PINK1 mutation in Taiwanese early-onset parkinsonism

Clinical, genetic, and dopamine transporter studies
  • Yi-Hsin Weng
  • Yah-Huei Wu Chou
  • Wen-Shiang Wu
  • Kun-Ju Lin
  • Hsiu-Chen Chang
  • Tzu-Chen Yen
  • Rou-Shayn Chen
  • Shiaw-Pyng Wey
  • Chin-Song Lu
ORIGINAL COMMUNICATION

DOI: 10.1007/s00415-007-0534-7

Cite this article as:
Weng, Y., Chou, Y.W., Wu, W. et al. J Neurol (2007) 254: 1347. doi:10.1007/s00415-007-0534-7

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 geneearly-onset Parkinson's diseasedopamine transporter99mTc-TRODAT-1 SPECT

Copyright information

© Steinkopff-Verlag 2007

Authors and Affiliations

  • Yi-Hsin Weng
    • 1
    • 5
  • Yah-Huei Wu Chou
    • 2
    • 5
  • Wen-Shiang Wu
    • 1
  • Kun-Ju Lin
    • 3
    • 5
  • Hsiu-Chen Chang
    • 1
  • Tzu-Chen Yen
    • 3
    • 5
  • Rou-Shayn Chen
    • 1
    • 5
  • Shiaw-Pyng Wey
    • 4
  • Chin-Song Lu
    • 1
    • 5
  1. 1.Neuroscience Research Center, Section of Movement Disorders, Dept. of NeurologyChang Gung Memorial Hospital and Chang Gung UniversityKweishan, TaoyuanTaiwan
  2. 2.Human Molecular Genetic LaboratoryChang Gung Memorial Hospital Chang Gung University College of MedicineKweishan, TaoyuanTaiwan
  3. 3.Dept. of Nuclear MedicineChang Gung Memorial Hospital Chang Gung University College of MedicineKweishan, TaoyuanTaiwan
  4. 4.Dept. of Medical Imaging and Radiological SciencesChang Gung Memorial Hospital Chang Gung University College of MedicineKweishan, TaoyuanTaiwan
  5. 5.Neuroscience Research CenterChang Gung Memorial Hospital, Chang Gung University College of MedicineChang Gung