GCH1 in Early-Onset Parkinson's Disease
Identifieur interne : 000793 ( PascalFrancis/Curation ); précédent : 000792; suivant : 000794GCH1 in Early-Onset Parkinson's Disease
Auteurs : Stephanie A. Cobb [États-Unis] ; Christian Wider [États-Unis] ; Owen A. Ross [États-Unis] ; Ignacio F. Mata [États-Unis] ; Charles H. Adler [États-Unis] ; Alex Rajput [Canada] ; Ali H. Rajput [Canada] ; Ruey-Meei Wu [Taïwan] ; Robert Hauser [États-Unis] ; Keith A. Josephs [États-Unis] ; Jonathan Carr [Afrique du Sud] ; Katrina Gwinn [États-Unis] ; Michael G. Heckman [États-Unis] ; Jan O. Aasly [Norvège] ; Timothy Lynch [Irlande (pays)] ; Ryan J. Uitti [États-Unis] ; Zbigniew K. Wszolek [États-Unis] ; Gregory Kapatos [États-Unis] ; Matthew J. Farrer [États-Unis]Source :
- Movement disorders [ 0885-3185 ] ; 2009.
Descripteurs français
- Pascal (Inist)
English descriptors
Abstract
Mutations in GTP-cyclohydrolase 1 (GCHI) 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 GCHI 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 GCHI locus in EOPD. However, our results further highlight the relevance of PRKN screening in familial EOPD.
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">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"><inist:fA14 i1="01"><s1>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>13 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Wider, Christian" sort="Wider, Christian" uniqKey="Wider C" first="Christian" last="Wider">Christian Wider</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>13 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Neurology, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Ross, Owen A" sort="Ross, Owen A" uniqKey="Ross O" first="Owen A." last="Ross">Owen A. Ross</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>13 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Mata, Ignacio F" sort="Mata, Ignacio F" uniqKey="Mata I" first="Ignacio F." last="Mata">Ignacio F. Mata</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Neurology, University of Washington School of Medicine</s1><s2>Seattle, Washington</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Adler, Charles H" sort="Adler, Charles H" uniqKey="Adler C" first="Charles H." last="Adler">Charles H. Adler</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Neurology, Mayo Clinic</s1><s2>Scottsdale, Arizona</s2><s3>USA</s3><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Rajput, Alex" sort="Rajput, Alex" uniqKey="Rajput A" first="Alex" last="Rajput">Alex Rajput</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Division of Neurology, Royal University Hospital, University of Saskatchewan</s1><s2>Saskatoon, Saskatchewan</s2><s3>CAN</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Rajput, Ali H" sort="Rajput, Ali H" uniqKey="Rajput A" first="Ali H." last="Rajput">Ali H. Rajput</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Division of Neurology, Royal University Hospital, University of Saskatchewan</s1><s2>Saskatoon, Saskatchewan</s2><s3>CAN</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Wu, Ruey Meei" sort="Wu, Ruey Meei" uniqKey="Wu R" first="Ruey-Meei" last="Wu">Ruey-Meei Wu</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University</s1><s2>Taipei</s2><s3>TWN</s3><sZ>8 aut.</sZ></inist:fA14><country>Taïwan</country></affiliation></author><author><name sortKey="Hauser, Robert" sort="Hauser, Robert" uniqKey="Hauser R" first="Robert" last="Hauser">Robert Hauser</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Department of Neurology, University of South Florida</s1><s2>Tampa, Florida</s2><s3>USA</s3><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></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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Heckman</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>13 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Aasly, Jan O" sort="Aasly, Jan O" uniqKey="Aasly J" first="Jan O." last="Aasly">Jan O. Aasly</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Department of Neuroscience, Norwegian University of Science and Technology</s1><s2>Trondheim</s2><s3>NOR</s3><sZ>14 aut.</sZ></inist:fA14><country>Norvège</country></affiliation></author><author><name sortKey="Lynch, Timothy" sort="Lynch, Timothy" uniqKey="Lynch T" first="Timothy" last="Lynch">Timothy Lynch</name><affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Dublin Neurological Institute at the Mater Misericordiae University Hospital</s1><s2>Dublin</s2><s3>IRL</s3><sZ>15 aut.</sZ></inist:fA14><country>Irlande (pays)</country></affiliation></author><author><name sortKey="Uitti, Ryan J" sort="Uitti, Ryan J" uniqKey="Uitti R" first="Ryan J." last="Uitti">Ryan J. Uitti</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Neurology, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Wszolek, Zbigniew K" sort="Wszolek, Zbigniew K" uniqKey="Wszolek Z" first="Zbigniew K." last="Wszolek">Zbigniew K. Wszolek</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Neurology, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Kapatos, Gregory" sort="Kapatos, Gregory" uniqKey="Kapatos G" first="Gregory" last="Kapatos">Gregory Kapatos</name><affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Center for Molecular Medicine and Genetics, Wayne State University School of Medicine</s1><s2>Detroit, Michigan</s2><s3>USA</s3><sZ>18 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J." last="Farrer">Matthew J. Farrer</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>13 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">09-0482370</idno><date when="2009">2009</date><idno type="stanalyst">PASCAL 09-0482370 INIST</idno><idno type="RBID">Pascal:09-0482370</idno><idno type="wicri:Area/PascalFrancis/Corpus">000499</idno><idno type="wicri:Area/PascalFrancis/Curation">000793</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">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"><inist:fA14 i1="01"><s1>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>13 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Wider, Christian" sort="Wider, Christian" uniqKey="Wider C" first="Christian" last="Wider">Christian Wider</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>13 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Neurology, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Ross, Owen A" sort="Ross, Owen A" uniqKey="Ross O" first="Owen A." last="Ross">Owen A. Ross</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>13 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Mata, Ignacio F" sort="Mata, Ignacio F" uniqKey="Mata I" first="Ignacio F." last="Mata">Ignacio F. Mata</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Neurology, University of Washington School of Medicine</s1><s2>Seattle, Washington</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Adler, Charles H" sort="Adler, Charles H" uniqKey="Adler C" first="Charles H." last="Adler">Charles H. Adler</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Neurology, Mayo Clinic</s1><s2>Scottsdale, Arizona</s2><s3>USA</s3><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Rajput, Alex" sort="Rajput, Alex" uniqKey="Rajput A" first="Alex" last="Rajput">Alex Rajput</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Division of Neurology, Royal University Hospital, University of Saskatchewan</s1><s2>Saskatoon, Saskatchewan</s2><s3>CAN</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Rajput, Ali H" sort="Rajput, Ali H" uniqKey="Rajput A" first="Ali H." last="Rajput">Ali H. Rajput</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Division of Neurology, Royal University Hospital, University of Saskatchewan</s1><s2>Saskatoon, Saskatchewan</s2><s3>CAN</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Wu, Ruey Meei" sort="Wu, Ruey Meei" uniqKey="Wu R" first="Ruey-Meei" last="Wu">Ruey-Meei Wu</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University</s1><s2>Taipei</s2><s3>TWN</s3><sZ>8 aut.</sZ></inist:fA14><country>Taïwan</country></affiliation></author><author><name sortKey="Hauser, Robert" sort="Hauser, Robert" uniqKey="Hauser R" first="Robert" last="Hauser">Robert Hauser</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Department of Neurology, University of South Florida</s1><s2>Tampa, Florida</s2><s3>USA</s3><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Josephs, Keith A" sort="Josephs, Keith A" uniqKey="Josephs K" first="Keith A." last="Josephs">Keith A. Josephs</name><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Department of Neurology, Mayo Clinic</s1><s2>Rochester, Minnesota</s2><s3>USA</s3><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Carr, Jonathan" sort="Carr, Jonathan" uniqKey="Carr J" first="Jonathan" last="Carr">Jonathan Carr</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Neurophysiology Laboratory, University of Stellenbosch, Tygerberg Hospital</s1><s2>Tygerberg</s2><s3>ZAF</s3><sZ>11 aut.</sZ></inist:fA14><country>Afrique du Sud</country></affiliation></author><author><name sortKey="Gwinn, Katrina" sort="Gwinn, Katrina" uniqKey="Gwinn K" first="Katrina" last="Gwinn">Katrina Gwinn</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Department of Molecular and Human Genetics, Baylor College of Medicine</s1><s2>Houston, Texas</s2><s3>USA</s3><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Heckman, Michael G" sort="Heckman, Michael G" uniqKey="Heckman M" first="Michael G." last="Heckman">Michael G. Heckman</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>13 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Aasly, Jan O" sort="Aasly, Jan O" uniqKey="Aasly J" first="Jan O." last="Aasly">Jan O. Aasly</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Department of Neuroscience, Norwegian University of Science and Technology</s1><s2>Trondheim</s2><s3>NOR</s3><sZ>14 aut.</sZ></inist:fA14><country>Norvège</country></affiliation></author><author><name sortKey="Lynch, Timothy" sort="Lynch, Timothy" uniqKey="Lynch T" first="Timothy" last="Lynch">Timothy Lynch</name><affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Dublin Neurological Institute at the Mater Misericordiae University Hospital</s1><s2>Dublin</s2><s3>IRL</s3><sZ>15 aut.</sZ></inist:fA14><country>Irlande (pays)</country></affiliation></author><author><name sortKey="Uitti, Ryan J" sort="Uitti, Ryan J" uniqKey="Uitti R" first="Ryan J." last="Uitti">Ryan J. Uitti</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Neurology, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Wszolek, Zbigniew K" sort="Wszolek, Zbigniew K" uniqKey="Wszolek Z" first="Zbigniew K." last="Wszolek">Zbigniew K. Wszolek</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Neurology, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Kapatos, Gregory" sort="Kapatos, Gregory" uniqKey="Kapatos G" first="Gregory" last="Kapatos">Gregory Kapatos</name><affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Center for Molecular Medicine and Genetics, Wayne State University School of Medicine</s1><s2>Detroit, Michigan</s2><s3>USA</s3><sZ>18 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J." last="Farrer">Matthew J. Farrer</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>13 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author></analytic><series><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Nervous system diseases</term><term>Parkinson disease</term><term>Segawa disease</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term><term>Pathologie du système nerveux</term><term>Maladie de Segawa</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mutations in GTP-cyclohydrolase 1 (GCHI) 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 GCHI 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 GCHI locus in EOPD. However, our results further highlight the relevance of PRKN screening in familial EOPD.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0885-3185</s0></fA01><fA03 i2="1"><s0>Mov. disord.</s0></fA03><fA05><s2>24</s2></fA05><fA06><s2>14</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>GCH1 in Early-Onset Parkinson's Disease</s1></fA08><fA11 i1="01" i2="1"><s1>COBB (Stephanie A.)</s1></fA11><fA11 i1="02" i2="1"><s1>WIDER (Christian)</s1></fA11><fA11 i1="03" i2="1"><s1>ROSS (Owen A.)</s1></fA11><fA11 i1="04" i2="1"><s1>MATA (Ignacio F.)</s1></fA11><fA11 i1="05" i2="1"><s1>ADLER (Charles H.)</s1></fA11><fA11 i1="06" i2="1"><s1>RAJPUT (Alex)</s1></fA11><fA11 i1="07" i2="1"><s1>RAJPUT (Ali H.)</s1></fA11><fA11 i1="08" i2="1"><s1>WU (Ruey-Meei)</s1></fA11><fA11 i1="09" i2="1"><s1>HAUSER (Robert)</s1></fA11><fA11 i1="10" i2="1"><s1>JOSEPHS (Keith A.)</s1></fA11><fA11 i1="11" i2="1"><s1>CARR (Jonathan)</s1></fA11><fA11 i1="12" i2="1"><s1>GWINN (Katrina)</s1></fA11><fA11 i1="13" i2="1"><s1>HECKMAN (Michael G.)</s1></fA11><fA11 i1="14" i2="1"><s1>AASLY (Jan O.)</s1></fA11><fA11 i1="15" i2="1"><s1>LYNCH (Timothy)</s1></fA11><fA11 i1="16" i2="1"><s1>UITTI (Ryan J.)</s1></fA11><fA11 i1="17" i2="1"><s1>WSZOLEK (Zbigniew K.)</s1></fA11><fA11 i1="18" i2="1"><s1>KAPATOS (Gregory)</s1></fA11><fA11 i1="19" i2="1"><s1>FARRER (Matthew J.)</s1></fA11><fA14 i1="01"><s1>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>13 aut.</sZ><sZ>19 aut.</sZ></fA14><fA14 i1="02"><s1>Department of Neurology, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ></fA14><fA14 i1="03"><s1>Department of Neurology, University of Washington School of Medicine</s1><s2>Seattle, Washington</s2><s3>USA</s3><sZ>4 aut.</sZ></fA14><fA14 i1="04"><s1>Department of Neurology, Mayo Clinic</s1><s2>Scottsdale, Arizona</s2><s3>USA</s3><sZ>5 aut.</sZ></fA14><fA14 i1="05"><s1>Division of Neurology, Royal University Hospital, University of Saskatchewan</s1><s2>Saskatoon, Saskatchewan</s2><s3>CAN</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ></fA14><fA14 i1="06"><s1>Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University</s1><s2>Taipei</s2><s3>TWN</s3><sZ>8 aut.</sZ></fA14><fA14 i1="07"><s1>Department of Neurology, University of South Florida</s1><s2>Tampa, Florida</s2><s3>USA</s3><sZ>9 aut.</sZ></fA14><fA14 i1="08"><s1>Department of Neurology, Mayo Clinic</s1><s2>Rochester, Minnesota</s2><s3>USA</s3><sZ>10 aut.</sZ></fA14><fA14 i1="09"><s1>Neurophysiology Laboratory, University of Stellenbosch, Tygerberg Hospital</s1><s2>Tygerberg</s2><s3>ZAF</s3><sZ>11 aut.</sZ></fA14><fA14 i1="10"><s1>Department of Molecular and Human Genetics, Baylor College of Medicine</s1><s2>Houston, Texas</s2><s3>USA</s3><sZ>12 aut.</sZ></fA14><fA14 i1="11"><s1>Department of Neuroscience, Norwegian University of Science and Technology</s1><s2>Trondheim</s2><s3>NOR</s3><sZ>14 aut.</sZ></fA14><fA14 i1="12"><s1>Dublin Neurological Institute at the Mater Misericordiae University Hospital</s1><s2>Dublin</s2><s3>IRL</s3><sZ>15 aut.</sZ></fA14><fA14 i1="13"><s1>Center for Molecular Medicine and Genetics, Wayne State University School of Medicine</s1><s2>Detroit, Michigan</s2><s3>USA</s3><sZ>18 aut.</sZ></fA14><fA20><s1>2070-2075</s1></fA20><fA21><s1>2009</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>20953</s2><s5>354000171427050050</s5></fA43><fA44><s0>0000</s0><s1>© 2009 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>25 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>09-0482370</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Movement disorders</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>Mutations in GTP-cyclohydrolase 1 (GCHI) 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 GCHI 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 GCHI locus in EOPD. However, our results further highlight the relevance of PRKN screening in familial EOPD.</s0></fC01><fC02 i1="01" i2="X"><s0>002B17</s0></fC02><fC02 i1="02" i2="X"><s0>002B17G</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Maladie de Parkinson</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Parkinson disease</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Parkinson enfermedad</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Pathologie du système nerveux</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Nervous system diseases</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Sistema nervioso patología</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Maladie de Segawa</s0><s4>CD</s4><s5>96</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Segawa disease</s0><s4>CD</s4><s5>96</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Segawa enfermedad</s0><s4>CD</s4><s5>96</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Pathologie de l'encéphale</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Cerebral disorder</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Encéfalo patología</s0><s5>37</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Syndrome extrapyramidal</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0><s5>38</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Maladie dégénérative</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Degenerative disease</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0><s5>39</s5></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Pathologie du système nerveux central</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Central nervous system disease</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0><s5>40</s5></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Maladie héréditaire</s0><s5>42</s5></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Genetic disease</s0><s5>42</s5></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Enfermedad hereditaria</s0><s5>42</s5></fC07><fN21><s1>348</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist></record>Pour manipuler ce document sous Unix (Dilib)
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