title: Analysis of Dosage Mutation in PARK2 among Korean Patients with Early-Onset or Familial Parkinson's Disease.
abstract: OBJECTIVE
  There is some controversy regarding heterozygous mutations of the gene encoding parkin (PARK2) as risk factors for Parkinson's disease (PD), and all previous studies have been performed in non-Asian populations. Dosage mutation of PARK2, rather than a point mutation or small insertion/deletion mutation, was reported to be a risk factor for familial PD; dosage mutation of PARK2 is common in Asian populations.
  
  
  METHODS
  We performed a gene-dosage analysis of PARK2 using real-time polymerase chain reaction for 189 patients with early-onset PD or familial PD, and 191 control individuals. In the case of PD patients with heterozygous gene-dosage mutation, we performed a sequencing analysis to exclude compound heterozygous mutations. The association between heterozygous mutation of PARK2 and PD was tested.
  
  
  RESULTS
  We identified 22 PD patients with PARK2 mutations (11.6%). Five patients (2.6%) had compound heterozygous mutations, and 13 patients (6.9%) had a heterozygous mutation. The phase could not be determined in one patient. Three small sequence variations were found in 30 mutated alleles (10.0%). Gene-dosage mutation accounted for 90% of all of the mutations found. The frequency of a heterozygous PARK2 gene-dosage mutation was higher in PD patients than in the controls.
  
  
  CONCLUSIONS
  Heterozygous gene-dosage mutation of PARK2 is a genetic risk factor for patients with early-onset or familial PD in Koreans.
authors.affiliation: Department of Neurology, Hallym University College of Medicine, Anyang, Korea.
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Chu
authors.affiliation: Department of Neurology, CHA University College of Medicine, Pocheon, Korea.
authors.forename: Won Chan
authors.initials: WC
authors.lastname: Kim
authors.affiliation: Ilsong Institute of Life Science, Hallym University, Anyang, Korea.
authors.forename: Jung Mi
authors.initials: JM
authors.lastname: Choi
authors.affiliation: Ilsong Institute of Life Science, Hallym University, Anyang, Korea.
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Hong
authors.affiliation: Department of Neurology, Hallym University College of Medicine, Anyang, Korea.
authors.forename: Suk Yun
authors.initials: SY
authors.lastname: Kang
authors.affiliation: Department of Neurology, Hallym University College of Medicine, Anyang, Korea.
authors.forename: Hyeo-Il
authors.initials: HI
authors.lastname: Ma
authors.affiliation: Department of Neurology, Hallym University College of Medicine, Anyang, Korea. ; Ilsong Institute of Life Science, Hallym University, Anyang, Korea. ; Hallym Institute of Translational Genomics and Bioinformatics, Hallym University Medical Center, Anyang, Korea.
authors.forename: Yun Joong
authors.initials: YJ
authors.lastname: Kim
keywords: PARK2; Parkinson's disease; gene-dosage change; risk factor