Analysis of Dosage Mutation in PARK2 among Korean Patients with Early-Onset or Familial Parkinson¡¯s Disease
Journal of Clinical Neurology 2014³â 10±Ç 3È£ p.244 ~ p.248
Áֹΰæ(Chu Min-Kyung) - Hallym University College of Medicine Department of Neurology
±è¿øÂù(Kim Won-Chan) - CHA University College of Medicine Department of Neurology
ÃÖÁ¤¹Ì(Choi Jung-Mi) - Hallym University Ilsong Institute of Life Science
È«Á¤ÈÆ(Hong Jeong-Hoon) - Hallym University Ilsong Institute of Life Science
°¼®À±(Kang Suk-Yun) - Hallym University College of Medicine Department of Neurology
¸¶È¿ÀÏ(Ma Hyeo-Il) - Hallym University College of Medicine Department of Neurology
±èÀ±Áß(Kim Yun-Joong) - Hallym University College of Medicine Department of Neurology
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.
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Parkinson¡¯s disease, PARK2, gene-dosage change, risk factor
KMID :
1130620140100030244
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