PINK1 mutations in sporadic early-onset Parkinson's disease.
Identifieur interne : 001576 ( Ncbi/Merge ); précédent : 001575; suivant : 001577PINK1 mutations in sporadic early-onset Parkinson's disease.
Auteurs : Eng-King Tan [Singapour] ; Kenneth Yew ; Eva Chua ; K. Puvan ; Hui Shen ; Esther Lee ; Kim-Yoong Puong ; Yi Zhao ; Ratnagopal Pavanni ; Meng-Cheong Wong ; Dominic Jamora ; Deidre De Silva ; Kyaw-Thu Moe ; Fung-Peng Woon ; Yih Yuen ; Louis TanSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2006.
Descripteurs français
- Wicri :
- geographic : Singapour.
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Protein Kinases.
- chemical : DNA Primers.
- geographic : Singapore.
- genetics : Asian Continental Ancestry Group, Parkinson Disease.
- Adult, Age of Onset, Base Sequence, Ethnic Groups, Heterozygote Detection, Homozygote, Humans, Middle Aged, Mutation.
Abstract
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.
DOI: 10.1002/mds.20810
PubMed: 16482571
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pubmed:16482571Le document en format XML
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<term>DNA Primers</term>
<term>Ethnic Groups</term>
<term>Heterozygote Detection</term>
<term>Homozygote</term>
<term>Humans</term>
<term>Middle Aged</term>
<term>Mutation</term>
<term>Parkinson Disease (genetics)</term>
<term>Protein Kinases (genetics)</term>
<term>Singapore</term>
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<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Protein Kinases</term>
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<front><div type="abstract" xml:lang="en">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.</div>
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<Abstract><AbstractText>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.</AbstractText>
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<country name="Singapour"><noRegion><name sortKey="Tan, Eng King" sort="Tan, Eng King" uniqKey="Tan E" first="Eng-King" last="Tan">Eng-King Tan</name>
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