PINK1 mutations in sporadic early-onset Parkinson's disease.
Pathogenic PINK1 mutations have been described in PARK6-linked Parkinson's disease (PD) patients of Asian origin. However, data on the frequency of PINK1 mutations in sporadic early-onset Parkinson's disease (EOPD) Asian patients are lacking. The objectives of this study were to report the frequency of PINK1 mutations of sporadic EOPD in an Asian cohort comprising of ethnic Chinese, Malays, and Indians, and to highlight a PINK1-positive patient who presented with restless legs symptoms. Eighty consecutive sporadic EOPD patients from the movement disorder clinics of two major tertiary institutions in the country were included. We performed sequence analysis of all the coding and exon-intron junctions of the PINK1 using specific primer sets. In addition, we genotyped polymorphisms detected from the analysis in a group of sporadic PD patients and controls. Three different mutations (two homozygous nonsense and one heterozygous missense) in the putative kinase domain were found in three patients, giving a 3.7% frequency of PINK1 mutations in our EOPD cohort. All the mutations were absent in 200 healthy controls. One patient with a novel homozygous nonsense PINK1 mutation presented unusually with restless legs symptoms. Separately, analysis of the frequency of four PINK1 polymorphisms in a group of sporadic PD and controls did not reveal any significant differences. We highlight a 3.7% frequency of PINK1 mutations in an Asian cohort (ethnic Chinese, Malay, and Indian) of EOPD. The phenotypic spectrum associated with PINK1-positive patients may be wider than previously reported. Polymorphisms of PINK1 do not appear to modulate risk of PD in our population.
Tan
Eng-King
EK
Division of Research, SingHealth, Singapore.
Yew
Kenneth
K
Chua
Eva
E
Puvan
K
K
Shen
Hui
H
Lee
Esther
E
Puong
Kim-Yoong
KY
Zhao
Yi
Y
Pavanni
Ratnagopal
R
Wong
Meng-Cheong
MC
Jamora
Dominic
D
de Silva
Deidre
D
Moe
Kyaw-Thu
KT
Woon
Fung-Peng
FP
Yuen
Yih
Y
Tan
Louis
L
D000328:Adult; D017668:Age of Onset; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers; D005006:Ethnicity; D006580:Genetic Carrier Screening; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics*; D012846:Singapore; D000099202:PTEN-Induced Putative Kinase
D017931:DNA Primers; D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase