Analysis of Dosage Mutation in PARK2 among Korean Patients with Early-Onset or Familial Parkinson’s Disease
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Background and Purpose There is some controversy regarding heterozygous mutations ofthe gene encoding parkin (PARK2) as risk factors for Parkinson’s disease (PD), and all previousstudies have been performed in non-Asian populations. Dosage mutation of PARK2, rather thana 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 chainreaction for 189 patients with early-onset PD or familial PD, and 191 control individuals. In thecase 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 foundin 30 mutated alleles (10.0%). Gene-dosage mutation accounted for 90% of all of the mutationsfound. The frequency of a heterozygous PARK2 gene-dosage mutation was higher in PD patientsthan 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.
Abstract
Background and Purpose There is some controversy regarding heterozygous mutations ofthe gene encoding parkin (PARK2) as risk factors for Parkinson’s disease (PD), and all previousstudies have been performed in non-Asian populations. Dosage mutation of PARK2, rather thana 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 chainreaction for 189 patients with early-onset PD or familial PD, and 191 control individuals. In thecase 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 foundin 30 mutated alleles (10.0%). Gene-dosage mutation accounted for 90% of all of the mutationsfound. The frequency of a heterozygous PARK2 gene-dosage mutation was higher in PD patientsthan 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.
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