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LRRK2 mutation in familial Parkinson’s disease in a Taiwanese population: clinical, PET, and functional studies

  • Original Paper
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Journal of Biomedical Science

Abstract

Pathogenic mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal-dominant familial Parkinson’s disease (PD). We performed clinical, imaging, and molecular functional studies in one family with the R1441H and six families with the G2385R variants of Lrrk2. To determine the contribution of these variants to familial PD in Taiwanese, we screened 32 Taiwanese or ethnic Chinese patients with familial PD for four pathogenic substitutions (R1441H, I2012T, I2020T, and G2019S) and one susceptibility polymorphism (G2385R). The frequencies of R1441H and G2385R were 3.7% and 22.2%, respectively. G2019S, I2012T, and I2020T were not detected. The clinical phenotypes and [18F]-dopa PET findings for subjects with R1441H or G2385R resembled those of patients with idiopathic PD; however, their lymphoblastoid cell lines showed increased apoptosis following exposure to a proteosome inhibitor. Thus, LRRK2 mutations are rare in Taiwanese with familial PD. Further study is needed to identify causative genes or unique biomarkers for familial PD.

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Acknowledgements

The authors thank Dr. Ignacio F Mata and Dr. Kachergus J for their support on some of the genotyping of DNA and Dr. Owen Ross for his critical review of the manuscript. We are grateful to The Taiwan National Science Council (NSC96-2628-B-002-102-MY3) and the National Taiwan University Hospital (96-M-006) for their support of this work. We would also like to thank all of the study participants.

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Authors and Affiliations

  1. Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei, 100, Taiwan

    Chin-Hsien Lin, Chun-Hwei Tai & Ruey-Meei Wu

  2. Department of Nuclear Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan

    Kai-Yuan Tzen

  3. Section of Neurology, Department of Internal Medicine, Taipei Hospital, Department of Health, Executive Yuan, Taiwan ROC

    Chin-Yi Yu

  4. Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, USA

    Matthew J. Farrer

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  1. Chin-Hsien Lin
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Correspondence to Ruey-Meei Wu.

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Lin, CH., Tzen, KY., Yu, CY. et al. LRRK2 mutation in familial Parkinson’s disease in a Taiwanese population: clinical, PET, and functional studies. J Biomed Sci 15, 661–667 (2008). https://doi.org/10.1007/s11373-008-9260-0

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  • DOI: https://doi.org/10.1007/s11373-008-9260-0

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