J Clin Neurol.  2014 Jul;10(3):244-248. 10.3988/jcn.2014.10.3.244.

Analysis of Dosage Mutation in PARK2 among Korean Patients with Early-Onset or Familial Parkinson's Disease

Affiliations
  • 1Department of Neurology, Hallym University College of Medicine, Anyang, Korea. yunkim@hallym.ac.kr
  • 2Department of Neurology, CHA University College of Medicine, Pocheon, Korea.
  • 3Ilsong Institute of Life Science, Hallym University, Anyang, Korea.
  • 4Hallym Institute of Translational Genomics and Bioinformatics, Hallym University Medical Center, Anyang, Korea.

Abstract

BACKGROUND AND PURPOSE
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.

Keyword

Parkinson's disease; PARK2; gene-dosage change; risk factor

MeSH Terms

Alleles
Asian Continental Ancestry Group
Humans
Parkinson Disease*
Point Mutation
Real-Time Polymerase Chain Reaction
Risk Factors

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