Original Article

Neurogenetics

, Volume 9, Issue 4, pp 263-269

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

  • Jung Mi ChoiAffiliated withDepartment of Neurology, Hallym University Sacred Heart Hospital, ILSONG Institute of Life Science, Hallym University
  • , Myoung Soo WooAffiliated withDepartment of Neurology, Hallym University Sacred Heart Hospital, ILSONG Institute of Life Science, Hallym University
  • , Hyeo-Il MaAffiliated withDepartment of Neurology, College of Medicine, Hallym University
  • , Suk Yun KangAffiliated withDepartment of Neurology, College of Medicine, Hallym University
  • , Young-Hee SungAffiliated withDepartment of Neurology, College of Medicine, Gachon University
  • , Seok Woo YongAffiliated withDepartment of Neurology, School of Medicine, Ajou University
  • , Sun Ju ChungAffiliated withDepartment of Neurology, Asan Medical Center, University of Ulsan College of Medicine
  • , Joong-Seok KimAffiliated withDepartment of Neurology, College of Medicine, The Catholic University of Korea
  • , Hae-won ShinAffiliated withDepartment of Neurology, College of Medicine, Yonsei University
    • , Chul Hyoung LyooAffiliated withDepartment of Neurology, College of Medicine, Yonsei University
    • , Phil Hyu LeeAffiliated withDepartment of Neurology, College of Medicine, Yonsei University
    • , Jong Sam BaikAffiliated withDepartment of Neurology, College of Medicine, Inje University
    • , Sang-Jin KimAffiliated withDepartment of Neurology, College of Medicine, Inje University
    • , Mee Young ParkAffiliated withDepartment of Neurology, College of Medicine, Yeungnam University
    • , Young Ho SohnAffiliated withDepartment of Neurology, College of Medicine, Yonsei University
    • , Jin-Ho KimAffiliated withDepartment of Neurology, Hallym University Sacred Heart Hospital, ILSONG Institute of Life Science, Hallym UniversityDepartment of Neurology, College of Medicine, Chosun University
    • , Jae Woo KimAffiliated withDepartment of Neurology, Hallym University Sacred Heart Hospital, ILSONG Institute of Life Science, Hallym UniversityDepartment of Neurology, College of Medicine, Dong-A University
    • , Myung Sik LeeAffiliated withDepartment of Neurology, College of Medicine, Yonsei University
    • , Myoung Chong LeeAffiliated withDepartment of Neurology, Asan Medical Center, University of Ulsan College of Medicine
    • , Dong-Hyun KimAffiliated withDepartment of Neurology, Hallym University Sacred Heart Hospital, ILSONG Institute of Life Science, Hallym UniversityDepartment of Social and Preventive Medicine, College of Medicine, Hallym University
    • , Yun Joong KimAffiliated withDepartment of Neurology, Hallym University Sacred Heart Hospital, ILSONG Institute of Life Science, Hallym UniversityDepartment of Neurology, College of Medicine, Hallym University Email author 

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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.

Keywords

Parkinson disease Genetics of Parkinson disease Mutation of Mendelian genes Susceptibility genes of Parkinson disease Early-onset Parkinson disease