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Analysis of PARK genes in a Korean cohort of early-onset Parkinson disease

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Abstract

Mutations in five PARK genes (SNCA, PARKIN, DJ-1, PINK1, and LRRK2) are well-established genetic causes of Parkinson disease (PD). Recently, G2385R substitution in LRRK2 has been determined as a susceptibility allele in Asian PD. The objective of this study is to determine the frequency of mutations in these PARK genes in a Korean early-onset Parkinson disease (EOPD) cohort. The authors sequenced 35 exons in SNCA, PARKIN, DJ-1, PINK1, and LRRK2 in 72 unrelated EOPD (age-at-onset ≤50) recruited from ten movement disorders clinics in South Korea. Gene dosage change of the aforementioned genes was studied using multiple ligation-dependent probe amplification. We found four patients with PARKIN mutations, which were homozygous deletion of exon 4, compound heterozygous deletion of exon 2 and exon 4, heterozygous deletion of exon 4, and heterozygous nonsense mutation (Q40X). Four patients had PINK1 mutations; a compound heterozygous mutation (N367S and K520RfsX522) and three heterozygous mutations (G32R, R279H, and F385L). A missense mutation of SNCA (A53T) was found in a familial PD with autosomal dominant inheritance. Nine patients (12.5%) had heterozygous G2385R polymorphism of LRRK2, whereas none had G2019S mutation. However, no mutations were detected in DJ-1 and UCHL1 in our series. We identified genetic variants in PARKIN, PINK1, LRRK2, and SNCA as a cause or genetic risk factors for PD in 25% of Korean EOPD, and mutation of PARKIN was the most common genetic cause.

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Acknowledgement

This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2005-042-E00123).

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Authors and Affiliations

  1. Department of Neurology, Hallym University Sacred Heart Hospital, ILSONG Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang-si, Gyeonggi-do, 431-061, Korea

    Jung Mi Choi, Myoung Soo Woo & Yun Joong Kim

  2. Department of Neurology, College of Medicine, Hallym University, Anyang-si, South Korea

    Hyeo-Il Ma, Suk Yun Kang & Yun Joong Kim

  3. Department of Neurology, College of Medicine, Gachon University, Incheon, South Korea

    Young-Hee Sung

  4. Department of Neurology, School of Medicine, Ajou University, Suwon, South Korea

    Seok Woo Yong

  5. Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

    Sun Ju Chung & Myoung Chong Lee

  6. Department of Neurology, College of Medicine, The Catholic University of Korea, Seoul, South Korea

    Joong-Seok Kim

  7. Department of Neurology, College of Medicine, Yonsei University, Seoul, South Korea

    Hae-won Shin, Chul Hyoung Lyoo, Phil Hyu Lee, Young Ho Sohn & Myung Sik Lee

  8. Department of Neurology, College of Medicine, Inje University, Gimhae, South Korea

    Jong Sam Baik & Sang-Jin Kim

  9. Department of Neurology, College of Medicine, Yeungnam University, Gyeongsan, South Korea

    Mee Young Park

  10. Department of Neurology, College of Medicine, Chosun University, Gwangju, South Korea

    Jin-Ho Kim

  11. Department of Neurology, College of Medicine, Dong-A University, Busan, South Korea

    Jae Woo Kim

  12. Department of Social and Preventive Medicine, College of Medicine, Hallym University, Anyang-si, South Korea

    Dong-Hyun Kim

Authors
  1. Jung Mi Choi
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  2. Myoung Soo Woo
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  11. Phil Hyu Lee
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  12. Jong Sam Baik
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  13. Sang-Jin Kim
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  14. Mee Young Park
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  15. Young Ho Sohn
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  16. Jin-Ho Kim
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  17. Jae Woo Kim
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  18. Myung Sik Lee
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  19. Myoung Chong Lee
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  20. Dong-Hyun Kim
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  21. Yun Joong Kim
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Corresponding author

Correspondence to Yun Joong Kim.

Additional information

Jung Mi Choi and Myoung Soo Woo equally contributed to this work.

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Choi, J.M., Woo, M.S., Ma, HI. et al. Analysis of PARK genes in a Korean cohort of early-onset Parkinson disease. Neurogenetics 9, 263–269 (2008). https://doi.org/10.1007/s10048-008-0138-0

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  • DOI: https://doi.org/10.1007/s10048-008-0138-0

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