title: Analysis of PARK genes in a Korean cohort of early-onset Parkinson disease.
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 <or=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.
authors.affiliation: Department of Neurology, Hallym University Sacred Heart Hospital, ILSONG Institute of Life Science, Hallym University, Dongan-gu, Anyang-si, Gyeonggi-do, Korea.
authors.forename: Jung Mi
authors.initials: JM
authors.lastname: Choi
authors.forename: Myoung Soo
authors.initials: MS
authors.lastname: Woo
authors.forename: Hyeo-Il
authors.initials: HI
authors.lastname: Ma
authors.forename: Suk Yun
authors.initials: SY
authors.lastname: Kang
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Sung
authors.forename: Seok Woo
authors.initials: SW
authors.lastname: Yong
authors.forename: Sun Ju
authors.initials: SJ
authors.lastname: Chung
authors.forename: Joong-Seok
authors.initials: JS
authors.lastname: Kim
authors.forename: Hae-won
authors.initials: HW
authors.lastname: Shin
authors.forename: Chul Hyoung
authors.initials: CH
authors.lastname: Lyoo
authors.forename: Phil Hyu
authors.initials: PH
authors.lastname: Lee
authors.forename: Jong Sam
authors.initials: JS
authors.lastname: Baik
authors.forename: Sang-Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Mee Young
authors.initials: MY
authors.lastname: Park
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Sohn
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Jae Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Myung Sik
authors.initials: MS
authors.lastname: Lee
authors.forename: Myoung Chong
authors.initials: MC
authors.lastname: Lee
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Yun Joong
authors.initials: YJ
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001483:Base Sequence; D016022:Case-Control Studies; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007723:Korea; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics*; D016133:Polymerase Chain Reaction; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D055815:Young Adult; D051844:alpha-Synuclein / Q000235:genetics; D000099202:PTEN-Induced Putative Kinase
chemical_list: D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; D000099202:PTEN-Induced Putative Kinase; C497604:SNCA protein, human; C111567:parkin protein; C495280:LRRK2 protein, human; C105131:PARK7 protein, human