Erschienen in:
01.10.2008 | Original Article
Analysis of PARK genes in a Korean cohort of early-onset Parkinson disease
verfasst von:
Jung Mi Choi, Myoung Soo Woo, Hyeo-Il Ma, Suk Yun Kang, Young-Hee Sung, Seok Woo Yong, Sun Ju Chung, Joong-Seok Kim, Hae-won Shin, Chul Hyoung Lyoo, Phil Hyu Lee, Jong Sam Baik, Sang-Jin Kim, Mee Young Park, Young Ho Sohn, Jin-Ho Kim, Jae Woo Kim, Myung Sik Lee, Myoung Chong Lee, Dong-Hyun Kim, Yun Joong Kim
Erschienen in:
Neurogenetics
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Ausgabe 4/2008
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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.