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PINK1 mutation in Taiwanese early-onset parkinsonism

Clinical, genetic, and dopamine transporter studies

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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.

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Authors and Affiliations

  1. Neuroscience Research Center, Section of Movement Disorders, Dept. of Neurology, Chang Gung Memorial Hospital and Chang Gung University, 33305, 5 Fu-Shin St., Kweishan, Taoyuan, Taiwan

    Yi-Hsin Weng, Wen-Shiang Wu Msc, Hsiu-Chen Chang BS,  Rou-Shayn Chen & Chin-Song Lu MD

  2. Human Molecular Genetic Laboratory, Chang Gung Memorial Hospital Chang Gung University College of Medicine, 33305, 5 Fu-Shin St., Kweishan, Taoyuan, Taiwan

    Yah-Huei Wu Chou

  3. Dept. of Nuclear Medicine, Chang Gung Memorial Hospital Chang Gung University College of Medicine, 33305, 5 Fu-Shin St., Kweishan, Taoyuan, Taiwan

    Kun-Ju Lin &  Tzu-Chen Yen

  4. Dept. of Medical Imaging and Radiological Sciences, Chang Gung Memorial Hospital Chang Gung University College of Medicine, 33305, 5 Fu-Shin St., Kweishan, Taoyuan, Taiwan

    Shiaw-Pyng Wey

  5. Neuroscience Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Chang Gung

    Yi-Hsin Weng,  Yah-Huei Wu Chou,  Kun-Ju Lin,  Tzu-Chen Yen,  Rou-Shayn Chen & Chin-Song Lu MD

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  1. Yi-Hsin Weng
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  2. Yah-Huei Wu Chou
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Correspondence to Chin-Song Lu MD.

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Weng, YH., Chou, YH.W., Wu, WS. et al. PINK1 mutation in Taiwanese early-onset parkinsonism. J Neurol 254, 1347–1355 (2007). https://doi.org/10.1007/s00415-007-0534-7

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  • DOI: https://doi.org/10.1007/s00415-007-0534-7

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