GCH1 in early-onset Parkinson's disease.
Identifieur interne : 002814 ( Ncbi/Checkpoint ); précédent : 002813; suivant : 002815GCH1 in early-onset Parkinson's disease.
Auteurs : Stephanie A. Cobb [États-Unis] ; Christian Wider ; Owen A. Ross ; Ignacio F. Mata ; Charles H. Adler ; Alex Rajput ; Ali H. Rajput ; Ruey-Meei Wu ; Robert Hauser ; Keith A. Josephs ; Jonathan Carr ; Katrina Gwinn ; Michael G. Heckman ; Jan O. Aasly ; Timothy Lynch ; Ryan J. Uitti ; Zbigniew K. Wszolek ; Gregory Kapatos ; Matthew J. FarrerSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2009.
English descriptors
- KwdEn :
- Adult, Age of Onset, Aged, Aged, 80 and over, DNA (genetics), DNA Mutational Analysis, European Continental Ancestry Group, Female, GTP Cyclohydrolase (genetics), Gene Dosage, Gene Frequency, Genetic Variation, Humans, Intracellular Signaling Peptides and Proteins (genetics), Male, Middle Aged, North America (epidemiology), Oncogene Proteins (genetics), Parkinson Disease (epidemiology), Parkinson Disease (genetics), Polymorphism, Single Nucleotide, Protein Kinases (genetics), Ubiquitin-Protein Ligases (genetics).
- MESH :
- chemical , genetics : DNA, GTP Cyclohydrolase, Intracellular Signaling Peptides and Proteins, Oncogene Proteins, Protein Kinases, Ubiquitin-Protein Ligases.
- geographic , epidemiology : North America.
- epidemiology : Parkinson Disease.
- genetics : Parkinson Disease.
- Adult, Age of Onset, Aged, Aged, 80 and over, DNA Mutational Analysis, European Continental Ancestry Group, Female, Gene Dosage, Gene Frequency, Genetic Variation, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide.
Abstract
Mutations in GTP-cyclohydrolase 1 (GCH1) cause autosomal dominant dopa-responsive dystonia (DRD), characterized by childhood-onset foot dystonia that later generalizes. DRD patients frequently present with associated Parkinsonism. Conversely, early-onset Parkinson's disease (EOPD) patients commonly display dystonia. Herein, we investigated the frequency of GCH1 mutations in a series of 53 familial EOPD patients (21 with dystonia) and screened them for mutations in PRKN, PINK1, and DJ-1. In addition, we examined a matched EOPD patient-control series for association of common variability at the GCH1 locus and EOPD susceptibility. No GCH1 coding change or copy-number abnormality was identified in familial EOPD patients. A novel 18-bp deletion was found in the proximal promoter (two patients, one control), which is expected to knock out two regulatory elements previously shown to regulate GCH1 transcription. No association was found between GCH1 variability and risk of EOPD. Fourteen (26.4%) familial EOPD patients had homozygous or compound heterozygous PRKN mutations. PRKN-positive patients were 10 years younger than PRKN-negative patients and had a twofold higher prevalence of dystonia. This study does not support a significant role for genetic variation at the GCH1 locus in EOPD. However, our results further highlight the relevance of PRKN screening in familial EOPD.
DOI: 10.1002/mds.22729
PubMed: 19735094
Affiliations:
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Ross</name></author><author><name sortKey="Mata, Ignacio F" sort="Mata, Ignacio F" uniqKey="Mata I" first="Ignacio F" last="Mata">Ignacio F. Mata</name></author><author><name sortKey="Adler, Charles H" sort="Adler, Charles H" uniqKey="Adler C" first="Charles H" last="Adler">Charles H. Adler</name></author><author><name sortKey="Rajput, Alex" sort="Rajput, Alex" uniqKey="Rajput A" first="Alex" last="Rajput">Alex Rajput</name></author><author><name sortKey="Rajput, Ali H" sort="Rajput, Ali H" uniqKey="Rajput A" first="Ali H" last="Rajput">Ali H. Rajput</name></author><author><name sortKey="Wu, Ruey Meei" sort="Wu, Ruey Meei" uniqKey="Wu R" first="Ruey-Meei" last="Wu">Ruey-Meei Wu</name></author><author><name sortKey="Hauser, Robert" sort="Hauser, Robert" uniqKey="Hauser R" first="Robert" last="Hauser">Robert Hauser</name></author><author><name sortKey="Josephs, Keith A" sort="Josephs, Keith A" uniqKey="Josephs K" first="Keith A" last="Josephs">Keith A. 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Farrer</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2009">2009</date><idno type="doi">10.1002/mds.22729</idno><idno type="RBID">pubmed:19735094</idno><idno type="pmid">19735094</idno><idno type="wicri:Area/PubMed/Corpus">001B65</idno><idno type="wicri:Area/PubMed/Curation">001B65</idno><idno type="wicri:Area/PubMed/Checkpoint">001E03</idno><idno type="wicri:Area/Ncbi/Merge">002814</idno><idno type="wicri:Area/Ncbi/Curation">002814</idno><idno type="wicri:Area/Ncbi/Checkpoint">002814</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">GCH1 in early-onset Parkinson's disease.</title><author><name sortKey="Cobb, Stephanie A" sort="Cobb, Stephanie A" uniqKey="Cobb S" first="Stephanie A" last="Cobb">Stephanie A. Cobb</name><affiliation wicri:level="1"><nlm:affiliation>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224</wicri:regionArea><wicri:noRegion>Florida 32224</wicri:noRegion></affiliation></author><author><name sortKey="Wider, Christian" sort="Wider, Christian" uniqKey="Wider C" first="Christian" last="Wider">Christian Wider</name></author><author><name sortKey="Ross, Owen A" sort="Ross, Owen A" uniqKey="Ross O" first="Owen A" last="Ross">Owen A. Ross</name></author><author><name sortKey="Mata, Ignacio F" sort="Mata, Ignacio F" uniqKey="Mata I" first="Ignacio F" last="Mata">Ignacio F. Mata</name></author><author><name sortKey="Adler, Charles H" sort="Adler, Charles H" uniqKey="Adler C" first="Charles H" last="Adler">Charles H. Adler</name></author><author><name sortKey="Rajput, Alex" sort="Rajput, Alex" uniqKey="Rajput A" first="Alex" last="Rajput">Alex Rajput</name></author><author><name sortKey="Rajput, Ali H" sort="Rajput, Ali H" uniqKey="Rajput A" first="Ali H" last="Rajput">Ali H. Rajput</name></author><author><name sortKey="Wu, Ruey Meei" sort="Wu, Ruey Meei" uniqKey="Wu R" first="Ruey-Meei" last="Wu">Ruey-Meei Wu</name></author><author><name sortKey="Hauser, Robert" sort="Hauser, Robert" uniqKey="Hauser R" first="Robert" last="Hauser">Robert Hauser</name></author><author><name sortKey="Josephs, Keith A" sort="Josephs, Keith A" uniqKey="Josephs K" first="Keith A" last="Josephs">Keith A. Josephs</name></author><author><name sortKey="Carr, Jonathan" sort="Carr, Jonathan" uniqKey="Carr J" first="Jonathan" last="Carr">Jonathan Carr</name></author><author><name sortKey="Gwinn, Katrina" sort="Gwinn, Katrina" uniqKey="Gwinn K" first="Katrina" last="Gwinn">Katrina Gwinn</name></author><author><name sortKey="Heckman, Michael G" sort="Heckman, Michael G" uniqKey="Heckman M" first="Michael G" last="Heckman">Michael G. Heckman</name></author><author><name sortKey="Aasly, Jan O" sort="Aasly, Jan O" uniqKey="Aasly J" first="Jan O" last="Aasly">Jan O. Aasly</name></author><author><name sortKey="Lynch, Timothy" sort="Lynch, Timothy" uniqKey="Lynch T" first="Timothy" last="Lynch">Timothy Lynch</name></author><author><name sortKey="Uitti, Ryan J" sort="Uitti, Ryan J" uniqKey="Uitti R" first="Ryan J" last="Uitti">Ryan J. Uitti</name></author><author><name sortKey="Wszolek, Zbigniew K" sort="Wszolek, Zbigniew K" uniqKey="Wszolek Z" first="Zbigniew K" last="Wszolek">Zbigniew K. Wszolek</name></author><author><name sortKey="Kapatos, Gregory" sort="Kapatos, Gregory" uniqKey="Kapatos G" first="Gregory" last="Kapatos">Gregory Kapatos</name></author><author><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J" last="Farrer">Matthew J. Farrer</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2009" type="published">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Age of Onset</term><term>Aged</term><term>Aged, 80 and over</term><term>DNA (genetics)</term><term>DNA Mutational Analysis</term><term>European Continental Ancestry Group</term><term>Female</term><term>GTP Cyclohydrolase (genetics)</term><term>Gene Dosage</term><term>Gene Frequency</term><term>Genetic Variation</term><term>Humans</term><term>Intracellular Signaling Peptides and Proteins (genetics)</term><term>Male</term><term>Middle Aged</term><term>North America (epidemiology)</term><term>Oncogene Proteins (genetics)</term><term>Parkinson Disease (epidemiology)</term><term>Parkinson Disease (genetics)</term><term>Polymorphism, Single Nucleotide</term><term>Protein Kinases (genetics)</term><term>Ubiquitin-Protein Ligases (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DNA</term><term>GTP Cyclohydrolase</term><term>Intracellular Signaling Peptides and Proteins</term><term>Oncogene Proteins</term><term>Protein Kinases</term><term>Ubiquitin-Protein Ligases</term></keywords><keywords scheme="MESH" type="geographic" qualifier="epidemiology" xml:lang="en"><term>North America</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Age of Onset</term><term>Aged</term><term>Aged, 80 and over</term><term>DNA Mutational Analysis</term><term>European Continental Ancestry Group</term><term>Female</term><term>Gene Dosage</term><term>Gene Frequency</term><term>Genetic Variation</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Polymorphism, Single Nucleotide</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mutations in GTP-cyclohydrolase 1 (GCH1) cause autosomal dominant dopa-responsive dystonia (DRD), characterized by childhood-onset foot dystonia that later generalizes. DRD patients frequently present with associated Parkinsonism. Conversely, early-onset Parkinson's disease (EOPD) patients commonly display dystonia. Herein, we investigated the frequency of GCH1 mutations in a series of 53 familial EOPD patients (21 with dystonia) and screened them for mutations in PRKN, PINK1, and DJ-1. In addition, we examined a matched EOPD patient-control series for association of common variability at the GCH1 locus and EOPD susceptibility. No GCH1 coding change or copy-number abnormality was identified in familial EOPD patients. A novel 18-bp deletion was found in the proximal promoter (two patients, one control), which is expected to knock out two regulatory elements previously shown to regulate GCH1 transcription. No association was found between GCH1 variability and risk of EOPD. Fourteen (26.4%) familial EOPD patients had homozygous or compound heterozygous PRKN mutations. PRKN-positive patients were 10 years younger than PRKN-negative patients and had a twofold higher prevalence of dystonia. This study does not support a significant role for genetic variation at the GCH1 locus in EOPD. However, our results further highlight the relevance of PRKN screening in familial EOPD.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><noCountry><name sortKey="Aasly, Jan O" sort="Aasly, Jan O" uniqKey="Aasly J" first="Jan O" last="Aasly">Jan O. Aasly</name><name sortKey="Adler, Charles H" sort="Adler, Charles H" uniqKey="Adler C" first="Charles H" last="Adler">Charles H. Adler</name><name sortKey="Carr, Jonathan" sort="Carr, Jonathan" uniqKey="Carr J" first="Jonathan" last="Carr">Jonathan Carr</name><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J" last="Farrer">Matthew J. Farrer</name><name sortKey="Gwinn, Katrina" sort="Gwinn, Katrina" uniqKey="Gwinn K" first="Katrina" last="Gwinn">Katrina Gwinn</name><name sortKey="Hauser, Robert" sort="Hauser, Robert" uniqKey="Hauser R" first="Robert" last="Hauser">Robert Hauser</name><name sortKey="Heckman, Michael G" sort="Heckman, Michael G" uniqKey="Heckman M" first="Michael G" last="Heckman">Michael G. Heckman</name><name sortKey="Josephs, Keith A" sort="Josephs, Keith A" uniqKey="Josephs K" first="Keith A" last="Josephs">Keith A. Josephs</name><name sortKey="Kapatos, Gregory" sort="Kapatos, Gregory" uniqKey="Kapatos G" first="Gregory" last="Kapatos">Gregory Kapatos</name><name sortKey="Lynch, Timothy" sort="Lynch, Timothy" uniqKey="Lynch T" first="Timothy" last="Lynch">Timothy Lynch</name><name sortKey="Mata, Ignacio F" sort="Mata, Ignacio F" uniqKey="Mata I" first="Ignacio F" last="Mata">Ignacio F. Mata</name><name sortKey="Rajput, Alex" sort="Rajput, Alex" uniqKey="Rajput A" first="Alex" last="Rajput">Alex Rajput</name><name sortKey="Rajput, Ali H" sort="Rajput, Ali H" uniqKey="Rajput A" first="Ali H" last="Rajput">Ali H. Rajput</name><name sortKey="Ross, Owen A" sort="Ross, Owen A" uniqKey="Ross O" first="Owen A" last="Ross">Owen A. Ross</name><name sortKey="Uitti, Ryan J" sort="Uitti, Ryan J" uniqKey="Uitti R" first="Ryan J" last="Uitti">Ryan J. Uitti</name><name sortKey="Wider, Christian" sort="Wider, Christian" uniqKey="Wider C" first="Christian" last="Wider">Christian Wider</name><name sortKey="Wszolek, Zbigniew K" sort="Wszolek, Zbigniew K" uniqKey="Wszolek Z" first="Zbigniew K" last="Wszolek">Zbigniew K. Wszolek</name><name sortKey="Wu, Ruey Meei" sort="Wu, Ruey Meei" uniqKey="Wu R" first="Ruey-Meei" last="Wu">Ruey-Meei Wu</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Cobb, Stephanie A" sort="Cobb, Stephanie A" uniqKey="Cobb S" first="Stephanie A" last="Cobb">Stephanie A. Cobb</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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