Analysis of PARK genes in a Korean cohort of early-onset Parkinson disease.
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.
Choi
Jung Mi
JM
Department of Neurology, Hallym University Sacred Heart Hospital, ILSONG Institute of Life Science, Hallym University, Dongan-gu, Anyang-si, Gyeonggi-do, Korea.
Woo
Myoung Soo
MS
Ma
Hyeo-Il
HI
Kang
Suk Yun
SY
Sung
Young-Hee
YH
Yong
Seok Woo
SW
Chung
Sun Ju
SJ
Kim
Joong-Seok
JS
Shin
Hae-won
HW
Lyoo
Chul Hyoung
CH
Lee
Phil Hyu
PH
Baik
Jong Sam
JS
Kim
Sang-Jin
SJ
Park
Mee Young
MY
Sohn
Young Ho
YH
Kim
Jin-Ho
JH
Kim
Jae Woo
JW
Lee
Myung Sik
MS
Lee
Myoung Chong
MC
Kim
Dong-Hyun
DH
Kim
Yun Joong
YJ
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
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