Motor phenotype of LRRK2 G2019S carriers in Early Onset Parkinson Disease
Identifieur interne : 000148 ( Pmc/Curation ); précédent : 000147; suivant : 000149Motor phenotype of LRRK2 G2019S carriers in Early Onset Parkinson Disease
Auteurs : Rn Alcalay [États-Unis] ; H. Mejia [États-Unis] ; M Tang [États-Unis] ; L. Rosado [États-Unis] ; M. Verbitsky [États-Unis] ; S. Kisselev [États-Unis] ; B. Ross [États-Unis] ; Ed Louis [États-Unis] ; C. Comella [États-Unis] ; A. Colcher [États-Unis] ; D. Jennings [États-Unis] ; M. Nance [États-Unis] ; S. Bressman [États-Unis] ; Wk Scott [États-Unis] ; C. Tanner [États-Unis] ; S. Mickel [États-Unis] ; H. Andrews [États-Unis] ; C. Waters [États-Unis] ; S. Fahn [États-Unis] ; L. Cote [États-Unis] ; S. Frucht [États-Unis] ; B. Ford [États-Unis] ; M. Rezak [États-Unis] ; K. Novak [États-Unis] ; Jh Friedman [États-Unis] ; R. Pfeiffer [États-Unis] ; L. Marsh [États-Unis] ; B. Hiner ; A. Siderowf [États-Unis] ; E. Caccappolo [États-Unis] ; R. Ottman [États-Unis] ; Ln Clark [États-Unis] ; K. Marder [États-Unis]Source :
- Archives of neurology [ 0003-9942 ] ; 2009.
Abstract
To determine the motor phenotype of
Cross sectional observational study
13 movement disorders centers
925 Early Onset Parkinson Disease (EOPD) cases defined as age at onset (AAO) ≤50.
Demographic information, family history of PD (FHPD), and the Unified Parkinson Disease Rating Scale (UPDRS) were collected on all participants. DNA samples were genotyped for
34 cases (3.7%) (14 previously reported) were G2019S carriers. No other mutations were found. Carriers were more likely to be AJ (55.9% vs. 11.9% p<0.001), but did not significantly differ in any other demographic or disease characteristics. Carriers had a lower tremor score (p=0.026) and were more likely to have a PIGD phenotype (92.3% vs. 58.9% p=0.003). The association of the G2019S mutation with PIGD phenotype remained after controlling for disease duration and AJ (OR= 17.7, p< 0.001).
EOPD G2019S
Url:
DOI: 10.1001/archneurol.2009.267
PubMed: 20008657
PubMed Central: 2837584
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Jh Friedman<affiliation><nlm:aff id="A18"> Department of Clinical Neurosciences, The Warren Alpert School of Medicine of Brown University, Providence, Rhode Island. USA</nlm:aff>
<wicri:noCountry code="subfield">Rhode Island. USA</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A23"> Medical College of Wisconsin, Milwaukee, Wisconsin USA</nlm:aff>
<wicri:noCountry code="subfield">Wisconsin USA</wicri:noCountry>
</affiliation>
Le document en format XML
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G2019S carriers in Early Onset Parkinson Disease</title>
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<author><name sortKey="Kisselev, S" sort="Kisselev, S" uniqKey="Kisselev S" first="S" last="Kisselev">S. Kisselev</name>
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<author><name sortKey="Louis, Ed" sort="Louis, Ed" uniqKey="Louis E" first="Ed" last="Louis">Ed Louis</name>
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<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
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<wicri:regionArea> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="A3"> Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
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<wicri:regionArea> Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="A4"> Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA</nlm:aff>
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<wicri:regionArea> Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY</wicri:regionArea>
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<author><name sortKey="Comella, C" sort="Comella, C" uniqKey="Comella C" first="C" last="Comella">C. Comella</name>
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<author><name sortKey="Colcher, A" sort="Colcher, A" uniqKey="Colcher A" first="A" last="Colcher">A. Colcher</name>
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<wicri:regionArea> Parkinson’s Disease and Movement Disorders Center, Pennsylvania Hospital, Philadelphia, Pennsylvania</wicri:regionArea>
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<wicri:regionArea> The Institute for Neurodegenerative Disorders, New Haven, Connecticut 06510-2716</wicri:regionArea>
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<author><name sortKey="Nance, M" sort="Nance, M" uniqKey="Nance M" first="M" last="Nance">M. Nance</name>
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<wicri:regionArea> Struthers Parkinson’s Center, Park Nicollet Clinic, Golden Valley, MN</wicri:regionArea>
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<wicri:regionArea> The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, New York, New York</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="A10"> Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA</nlm:aff>
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<wicri:regionArea> Department of Neurology, Albert Einstein College of Medicine, Bronx, New York</wicri:regionArea>
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<author><name sortKey="Scott, Wk" sort="Scott, Wk" uniqKey="Scott W" first="Wk" last="Scott">Wk Scott</name>
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<wicri:regionArea> Dr. John T Macdonald Foundation, Department of Human Genetics, Miami Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL 33136</wicri:regionArea>
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<author><name sortKey="Tanner, C" sort="Tanner, C" uniqKey="Tanner C" first="C" last="Tanner">C. Tanner</name>
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<wicri:regionArea> Parkinson’s Institute, Sunnyvale, California</wicri:regionArea>
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<author><name sortKey="Mickel, S" sort="Mickel, S" uniqKey="Mickel S" first="S" last="Mickel">S. Mickel</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Marshfield Clinic, Department of Neurology, Marshfield, WI 54449</wicri:regionArea>
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<author><name sortKey="Andrews, H" sort="Andrews, H" uniqKey="Andrews H" first="H" last="Andrews">H. Andrews</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> New York State Psychiatric Institute, Data Coordinating Center, New York, NY</wicri:regionArea>
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<author><name sortKey="Waters, C" sort="Waters, C" uniqKey="Waters C" first="C" last="Waters">C. Waters</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
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<author><name sortKey="Fahn, S" sort="Fahn, S" uniqKey="Fahn S" first="S" last="Fahn">S. Fahn</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
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<author><name sortKey="Cote, L" sort="Cote, L" uniqKey="Cote L" first="L" last="Cote">L. Cote</name>
<affiliation wicri:level="1"><nlm:aff id="A3"> Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
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<author><name sortKey="Frucht, S" sort="Frucht, S" uniqKey="Frucht S" first="S" last="Frucht">S. Frucht</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ford, B" sort="Ford, B" uniqKey="Ford B" first="B" last="Ford">B. Ford</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Rezak, M" sort="Rezak, M" uniqKey="Rezak M" first="M" last="Rezak">M. Rezak</name>
<affiliation wicri:level="1"><nlm:aff id="A15"> Department of Neurology, at NorthShore University HealthSystem, Evanston, Illinois, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, at NorthShore University HealthSystem, Evanston, Illinois</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A16"> Department of Neurology, at Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, at Northwestern University, Feinberg School of Medicine, Chicago, Illinois</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Novak, K" sort="Novak, K" uniqKey="Novak K" first="K" last="Novak">K. Novak</name>
<affiliation wicri:level="1"><nlm:aff id="A15"> Department of Neurology, at NorthShore University HealthSystem, Evanston, Illinois, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, at NorthShore University HealthSystem, Evanston, Illinois</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A16"> Department of Neurology, at Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, at Northwestern University, Feinberg School of Medicine, Chicago, Illinois</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Friedman, Jh" sort="Friedman, Jh" uniqKey="Friedman J" first="Jh" last="Friedman">Jh Friedman</name>
<affiliation wicri:level="2"><nlm:aff id="A17"> Parkinson’s Disease and Movement Disorders Center of NeuroHealth, Warwick, Rhode Island</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Rhode Island</region>
</placeName>
<wicri:cityArea> Parkinson’s Disease and Movement Disorders Center of NeuroHealth, Warwick</wicri:cityArea>
</affiliation>
<affiliation><nlm:aff id="A18"> Department of Clinical Neurosciences, The Warren Alpert School of Medicine of Brown University, Providence, Rhode Island. USA</nlm:aff>
<wicri:noCountry code="subfield">Rhode Island. USA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Pfeiffer, R" sort="Pfeiffer, R" uniqKey="Pfeiffer R" first="R" last="Pfeiffer">R. Pfeiffer</name>
<affiliation wicri:level="1"><nlm:aff id="A19"> Department of Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Marsh, L" sort="Marsh, L" uniqKey="Marsh L" first="L" last="Marsh">L. Marsh</name>
<affiliation wicri:level="1"><nlm:aff id="A20"> Morris K. Udall Parkinson’s Disease Research Center of Excellence, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Morris K. Udall Parkinson’s Disease Research Center of Excellence, Johns Hopkins University School of Medicine, Baltimore, Maryland</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A21"> Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine, Baltimore, Maryland, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine, Baltimore, Maryland</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A22"> Department of Neurology and Neurological Sciences Johns Hopkins University School of Medicine, Baltimore, Maryland, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology and Neurological Sciences Johns Hopkins University School of Medicine, Baltimore, Maryland</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hiner, B" sort="Hiner, B" uniqKey="Hiner B" first="B" last="Hiner">B. Hiner</name>
<affiliation><nlm:aff id="A23"> Medical College of Wisconsin, Milwaukee, Wisconsin USA</nlm:aff>
<wicri:noCountry code="subfield">Wisconsin USA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Siderowf, A" sort="Siderowf, A" uniqKey="Siderowf A" first="A" last="Siderowf">A. Siderowf</name>
<affiliation wicri:level="1"><nlm:aff id="A24"> Department of Neurology, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, University of Pennsylvania Health System, Philadelphia, Pennsylvania</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Caccappolo, E" sort="Caccappolo, E" uniqKey="Caccappolo E" first="E" last="Caccappolo">E. Caccappolo</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A2"> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ottman, R" sort="Ottman, R" uniqKey="Ottman R" first="R" last="Ottman">R. Ottman</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A3"> Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A4"> Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Clark, Ln" sort="Clark, Ln" uniqKey="Clark L" first="Ln" last="Clark">Ln Clark</name>
<affiliation wicri:level="1"><nlm:aff id="A2"> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A25"> Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A26"> Center for Human Genetics, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Center for Human Genetics, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Marder, K" sort="Marder, K" uniqKey="Marder K" first="K" last="Marder">K. Marder</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A2"> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A3"> Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A27"> Department of Psychiatry, Columbia University Medical Center, NYC, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Psychiatry, Columbia University Medical Center, NYC, NY</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">20008657</idno>
<idno type="pmc">2837584</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837584</idno>
<idno type="RBID">PMC:2837584</idno>
<idno type="doi">10.1001/archneurol.2009.267</idno>
<date when="2009">2009</date>
<idno type="wicri:Area/Pmc/Corpus">000148</idno>
<idno type="wicri:Area/Pmc/Curation">000148</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Motor phenotype of <italic>LRRK2</italic>
G2019S carriers in Early Onset Parkinson Disease</title>
<author><name sortKey="Alcalay, Rn" sort="Alcalay, Rn" uniqKey="Alcalay R" first="Rn" last="Alcalay">Rn Alcalay</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mejia Santana, H" sort="Mejia Santana, H" uniqKey="Mejia Santana H" first="H" last="Mejia">H. Mejia</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tang, M X" sort="Tang, M X" uniqKey="Tang M" first="M" last="Tang">M Tang</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A2"> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Rosado, L" sort="Rosado, L" uniqKey="Rosado L" first="L" last="Rosado">L. Rosado</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Verbitsky, M" sort="Verbitsky, M" uniqKey="Verbitsky M" first="M" last="Verbitsky">M. Verbitsky</name>
<affiliation wicri:level="1"><nlm:aff id="A2"> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kisselev, S" sort="Kisselev, S" uniqKey="Kisselev S" first="S" last="Kisselev">S. Kisselev</name>
<affiliation wicri:level="1"><nlm:aff id="A2"> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ross, B" sort="Ross, B" uniqKey="Ross B" first="B" last="Ross">B. Ross</name>
<affiliation wicri:level="1"><nlm:aff id="A2"> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Louis, Ed" sort="Louis, Ed" uniqKey="Louis E" first="Ed" last="Louis">Ed Louis</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A2"> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A3"> Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A4"> Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Comella, C" sort="Comella, C" uniqKey="Comella C" first="C" last="Comella">C. Comella</name>
<affiliation wicri:level="1"><nlm:aff id="A5"> Department of Neurology/Movement Disorder Section, Chicago, IL, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology/Movement Disorder Section, Chicago, IL</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Colcher, A" sort="Colcher, A" uniqKey="Colcher A" first="A" last="Colcher">A. Colcher</name>
<affiliation wicri:level="1"><nlm:aff id="A6"> Parkinson’s Disease and Movement Disorders Center, Pennsylvania Hospital, Philadelphia, Pennsylvania, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Parkinson’s Disease and Movement Disorders Center, Pennsylvania Hospital, Philadelphia, Pennsylvania</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Jennings, D" sort="Jennings, D" uniqKey="Jennings D" first="D" last="Jennings">D. Jennings</name>
<affiliation wicri:level="1"><nlm:aff id="A7"> The Institute for Neurodegenerative Disorders, New Haven, Connecticut 06510-2716, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> The Institute for Neurodegenerative Disorders, New Haven, Connecticut 06510-2716</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Nance, M" sort="Nance, M" uniqKey="Nance M" first="M" last="Nance">M. Nance</name>
<affiliation wicri:level="1"><nlm:aff id="A8"> Struthers Parkinson’s Center, Park Nicollet Clinic, Golden Valley, MN, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Struthers Parkinson’s Center, Park Nicollet Clinic, Golden Valley, MN</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bressman, S" sort="Bressman, S" uniqKey="Bressman S" first="S" last="Bressman">S. Bressman</name>
<affiliation wicri:level="1"><nlm:aff id="A9"> The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, New York, New York, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, New York, New York</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A10"> Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, Albert Einstein College of Medicine, Bronx, New York</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Scott, Wk" sort="Scott, Wk" uniqKey="Scott W" first="Wk" last="Scott">Wk Scott</name>
<affiliation wicri:level="1"><nlm:aff id="A11"> Dr. John T Macdonald Foundation, Department of Human Genetics, Miami Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Dr. John T Macdonald Foundation, Department of Human Genetics, Miami Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL 33136</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tanner, C" sort="Tanner, C" uniqKey="Tanner C" first="C" last="Tanner">C. Tanner</name>
<affiliation wicri:level="1"><nlm:aff id="A12"> Parkinson’s Institute, Sunnyvale, California, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Parkinson’s Institute, Sunnyvale, California</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mickel, S" sort="Mickel, S" uniqKey="Mickel S" first="S" last="Mickel">S. Mickel</name>
<affiliation wicri:level="1"><nlm:aff id="A13"> Marshfield Clinic, Department of Neurology, Marshfield, WI 54449, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Marshfield Clinic, Department of Neurology, Marshfield, WI 54449</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Andrews, H" sort="Andrews, H" uniqKey="Andrews H" first="H" last="Andrews">H. Andrews</name>
<affiliation wicri:level="1"><nlm:aff id="A14"> New York State Psychiatric Institute, Data Coordinating Center, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> New York State Psychiatric Institute, Data Coordinating Center, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Waters, C" sort="Waters, C" uniqKey="Waters C" first="C" last="Waters">C. Waters</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Fahn, S" sort="Fahn, S" uniqKey="Fahn S" first="S" last="Fahn">S. Fahn</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Cote, L" sort="Cote, L" uniqKey="Cote L" first="L" last="Cote">L. Cote</name>
<affiliation wicri:level="1"><nlm:aff id="A3"> Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Frucht, S" sort="Frucht, S" uniqKey="Frucht S" first="S" last="Frucht">S. Frucht</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ford, B" sort="Ford, B" uniqKey="Ford B" first="B" last="Ford">B. Ford</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Rezak, M" sort="Rezak, M" uniqKey="Rezak M" first="M" last="Rezak">M. Rezak</name>
<affiliation wicri:level="1"><nlm:aff id="A15"> Department of Neurology, at NorthShore University HealthSystem, Evanston, Illinois, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, at NorthShore University HealthSystem, Evanston, Illinois</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A16"> Department of Neurology, at Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, at Northwestern University, Feinberg School of Medicine, Chicago, Illinois</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Novak, K" sort="Novak, K" uniqKey="Novak K" first="K" last="Novak">K. Novak</name>
<affiliation wicri:level="1"><nlm:aff id="A15"> Department of Neurology, at NorthShore University HealthSystem, Evanston, Illinois, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, at NorthShore University HealthSystem, Evanston, Illinois</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A16"> Department of Neurology, at Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, at Northwestern University, Feinberg School of Medicine, Chicago, Illinois</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Friedman, Jh" sort="Friedman, Jh" uniqKey="Friedman J" first="Jh" last="Friedman">Jh Friedman</name>
<affiliation wicri:level="2"><nlm:aff id="A17"> Parkinson’s Disease and Movement Disorders Center of NeuroHealth, Warwick, Rhode Island</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Rhode Island</region>
</placeName>
<wicri:cityArea> Parkinson’s Disease and Movement Disorders Center of NeuroHealth, Warwick</wicri:cityArea>
</affiliation>
<affiliation><nlm:aff id="A18"> Department of Clinical Neurosciences, The Warren Alpert School of Medicine of Brown University, Providence, Rhode Island. USA</nlm:aff>
<wicri:noCountry code="subfield">Rhode Island. USA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Pfeiffer, R" sort="Pfeiffer, R" uniqKey="Pfeiffer R" first="R" last="Pfeiffer">R. Pfeiffer</name>
<affiliation wicri:level="1"><nlm:aff id="A19"> Department of Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Marsh, L" sort="Marsh, L" uniqKey="Marsh L" first="L" last="Marsh">L. Marsh</name>
<affiliation wicri:level="1"><nlm:aff id="A20"> Morris K. Udall Parkinson’s Disease Research Center of Excellence, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Morris K. Udall Parkinson’s Disease Research Center of Excellence, Johns Hopkins University School of Medicine, Baltimore, Maryland</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A21"> Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine, Baltimore, Maryland, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine, Baltimore, Maryland</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A22"> Department of Neurology and Neurological Sciences Johns Hopkins University School of Medicine, Baltimore, Maryland, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology and Neurological Sciences Johns Hopkins University School of Medicine, Baltimore, Maryland</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hiner, B" sort="Hiner, B" uniqKey="Hiner B" first="B" last="Hiner">B. Hiner</name>
<affiliation><nlm:aff id="A23"> Medical College of Wisconsin, Milwaukee, Wisconsin USA</nlm:aff>
<wicri:noCountry code="subfield">Wisconsin USA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Siderowf, A" sort="Siderowf, A" uniqKey="Siderowf A" first="A" last="Siderowf">A. Siderowf</name>
<affiliation wicri:level="1"><nlm:aff id="A24"> Department of Neurology, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, University of Pennsylvania Health System, Philadelphia, Pennsylvania</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Caccappolo, E" sort="Caccappolo, E" uniqKey="Caccappolo E" first="E" last="Caccappolo">E. Caccappolo</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A2"> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ottman, R" sort="Ottman, R" uniqKey="Ottman R" first="R" last="Ottman">R. Ottman</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A3"> Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A4"> Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Clark, Ln" sort="Clark, Ln" uniqKey="Clark L" first="Ln" last="Clark">Ln Clark</name>
<affiliation wicri:level="1"><nlm:aff id="A2"> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A25"> Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A26"> Center for Human Genetics, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Center for Human Genetics, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Marder, K" sort="Marder, K" uniqKey="Marder K" first="K" last="Marder">K. Marder</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A2"> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A3"> Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A27"> Department of Psychiatry, Columbia University Medical Center, NYC, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> Department of Psychiatry, Columbia University Medical Center, NYC, NY</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Archives of neurology</title>
<idno type="ISSN">0003-9942</idno>
<idno type="e-ISSN">1538-3687</idno>
<imprint><date when="2009">2009</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Objective</title>
<p id="P1">To determine the motor phenotype of <italic>LRRK2</italic>
G2019S mutation carriers</p>
</sec>
<sec id="S2"><title>Background</title>
<p id="P2"><italic>LRRK2</italic>
mutation carriers were previously reported to manifest the tremor-dominant (TD) motor phenotype, which has been associated with slower motor progression and less cognitive impairment compared to the postural instability gait difficulty (PIGD) phenotype.</p>
</sec>
<sec id="S3"><title>Design</title>
<p id="P3">Cross sectional observational study</p>
</sec>
<sec id="S4"><title>Setting</title>
<p id="P4">13 movement disorders centers</p>
</sec>
<sec id="S5"><title>Participants</title>
<p id="P5">925 Early Onset Parkinson Disease (EOPD) cases defined as age at onset (AAO) ≤50.</p>
</sec>
<sec id="S6"><title>Main Outcome Measures</title>
<p id="P6"><italic>LRRK2</italic>
mutation status and PD motor phenotype: TD or PIGD</p>
</sec>
<sec sec-type="methods" id="S7"><title>Methods</title>
<p id="P7">Demographic information, family history of PD (FHPD), and the Unified Parkinson Disease Rating Scale (UPDRS) were collected on all participants. DNA samples were genotyped for <italic>LRRK2</italic>
mutations (G2019S, I2020T, R1441C and Y1699C). Logistic regression was used to examine associations of G2019S mutation status with motor phenotype adjusting for disease duration, Ashkenazi Jewish (AJ) ancestry, levodopa dose, and FHPD.</p>
</sec>
<sec id="S8"><title>Results</title>
<p id="P8">34 cases (3.7%) (14 previously reported) were G2019S carriers. No other mutations were found. Carriers were more likely to be AJ (55.9% vs. 11.9% p<0.001), but did not significantly differ in any other demographic or disease characteristics. Carriers had a lower tremor score (p=0.026) and were more likely to have a PIGD phenotype (92.3% vs. 58.9% p=0.003). The association of the G2019S mutation with PIGD phenotype remained after controlling for disease duration and AJ (OR= 17.7, p< 0.001).</p>
</sec>
<sec id="S9"><title>Conclusion</title>
<p id="P9">EOPD G2019S <italic>LRRK2</italic>
carriers are more likely to manifest the PIGD phenotype, which may have implications for disease course.</p>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0372436</journal-id>
<journal-id journal-id-type="pubmed-jr-id">804</journal-id>
<journal-id journal-id-type="nlm-ta">Arch Neurol</journal-id>
<journal-title>Archives of neurology</journal-title>
<issn pub-type="ppub">0003-9942</issn>
<issn pub-type="epub">1538-3687</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">20008657</article-id>
<article-id pub-id-type="pmc">2837584</article-id>
<article-id pub-id-type="doi">10.1001/archneurol.2009.267</article-id>
<article-id pub-id-type="manuscript">NIHMS179680</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Motor phenotype of <italic>LRRK2</italic>
G2019S carriers in Early Onset Parkinson Disease</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Alcalay</surname>
<given-names>RN</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mejia-Santana</surname>
<given-names>H</given-names>
</name>
<degrees>MSc</degrees>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tang</surname>
<given-names>M-X</given-names>
</name>
<degrees>PhD</degrees>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="A2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rosado</surname>
<given-names>L</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Verbitsky</surname>
<given-names>M</given-names>
</name>
<degrees>PhD</degrees>
<xref rid="A2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kisselev</surname>
<given-names>S</given-names>
</name>
<degrees>MS</degrees>
<xref rid="A2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ross</surname>
<given-names>B</given-names>
</name>
<degrees>BSc</degrees>
<xref rid="A2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Louis</surname>
<given-names>ED</given-names>
</name>
<degrees>MD, MSc</degrees>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="A2" ref-type="aff">2</xref>
<xref rid="A3" ref-type="aff">3</xref>
<xref rid="A4" ref-type="aff">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Comella</surname>
<given-names>C</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A5" ref-type="aff">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Colcher</surname>
<given-names>A</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A6" ref-type="aff">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jennings</surname>
<given-names>D</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A7" ref-type="aff">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nance</surname>
<given-names>M</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A8" ref-type="aff">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bressman</surname>
<given-names>S</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A9" ref-type="aff">9</xref>
<xref rid="A10" ref-type="aff">10</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Scott</surname>
<given-names>WK</given-names>
</name>
<degrees>PhD</degrees>
<xref rid="A11" ref-type="aff">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tanner</surname>
<given-names>C</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref rid="A12" ref-type="aff">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mickel</surname>
<given-names>S</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A13" ref-type="aff">13</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Andrews</surname>
<given-names>H</given-names>
</name>
<degrees>PhD</degrees>
<xref rid="A14" ref-type="aff">14</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Waters</surname>
<given-names>C</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Fahn</surname>
<given-names>S</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cote</surname>
<given-names>L</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A3" ref-type="aff">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Frucht</surname>
<given-names>S</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ford</surname>
<given-names>B</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rezak</surname>
<given-names>M</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref rid="A15" ref-type="aff">15</xref>
<xref rid="A16" ref-type="aff">16</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Novak</surname>
<given-names>K</given-names>
</name>
<degrees>PhD</degrees>
<xref rid="A15" ref-type="aff">15</xref>
<xref rid="A16" ref-type="aff">16</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Friedman</surname>
<given-names>JH</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A17" ref-type="aff">17</xref>
<xref rid="A18" ref-type="aff">18</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pfeiffer</surname>
<given-names>R</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A19" ref-type="aff">19</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Marsh</surname>
<given-names>L</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A20" ref-type="aff">20</xref>
<xref rid="A21" ref-type="aff">21</xref>
<xref rid="A22" ref-type="aff">22</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hiner</surname>
<given-names>B</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A23" ref-type="aff">23</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Siderowf</surname>
<given-names>A</given-names>
</name>
<degrees>MD, MSCE</degrees>
<xref rid="A24" ref-type="aff">24</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Caccappolo</surname>
<given-names>E</given-names>
</name>
<degrees>PhD</degrees>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="A2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ottman</surname>
<given-names>R</given-names>
</name>
<degrees>PhD</degrees>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="A3" ref-type="aff">3</xref>
<xref rid="A4" ref-type="aff">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Clark</surname>
<given-names>LN</given-names>
</name>
<degrees>PhD</degrees>
<xref rid="A2" ref-type="aff">2</xref>
<xref rid="A25" ref-type="aff">25</xref>
<xref rid="A26" ref-type="aff">26</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Marder</surname>
<given-names>K</given-names>
</name>
<degrees>MD, MPH</degrees>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="A2" ref-type="aff">2</xref>
<xref rid="A3" ref-type="aff">3</xref>
<xref rid="A27" ref-type="aff">27</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</aff>
<aff id="A2"><label>2</label>
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA</aff>
<aff id="A3"><label>3</label>
Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA</aff>
<aff id="A4"><label>4</label>
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA</aff>
<aff id="A5"><label>5</label>
Department of Neurology/Movement Disorder Section, Chicago, IL, USA</aff>
<aff id="A6"><label>6</label>
Parkinson’s Disease and Movement Disorders Center, Pennsylvania Hospital, Philadelphia, Pennsylvania, USA</aff>
<aff id="A7"><label>7</label>
The Institute for Neurodegenerative Disorders, New Haven, Connecticut 06510-2716, USA</aff>
<aff id="A8"><label>8</label>
Struthers Parkinson’s Center, Park Nicollet Clinic, Golden Valley, MN, USA</aff>
<aff id="A9"><label>9</label>
The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, New York, New York, USA</aff>
<aff id="A10"><label>10</label>
Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA</aff>
<aff id="A11"><label>11</label>
Dr. John T Macdonald Foundation, Department of Human Genetics, Miami Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA</aff>
<aff id="A12"><label>12</label>
Parkinson’s Institute, Sunnyvale, California, USA</aff>
<aff id="A13"><label>13</label>
Marshfield Clinic, Department of Neurology, Marshfield, WI 54449, USA</aff>
<aff id="A14"><label>14</label>
New York State Psychiatric Institute, Data Coordinating Center, New York, NY, USA</aff>
<aff id="A15"><label>15</label>
Department of Neurology, at NorthShore University HealthSystem, Evanston, Illinois, USA</aff>
<aff id="A16"><label>16</label>
Department of Neurology, at Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA</aff>
<aff id="A17"><label>17</label>
Parkinson’s Disease and Movement Disorders Center of NeuroHealth, Warwick, Rhode Island</aff>
<aff id="A18"><label>18</label>
Department of Clinical Neurosciences, The Warren Alpert School of Medicine of Brown University, Providence, Rhode Island. USA</aff>
<aff id="A19"><label>19</label>
Department of Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA</aff>
<aff id="A20"><label>20</label>
Morris K. Udall Parkinson’s Disease Research Center of Excellence, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA</aff>
<aff id="A21"><label>21</label>
Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine, Baltimore, Maryland, USA</aff>
<aff id="A22"><label>22</label>
Department of Neurology and Neurological Sciences Johns Hopkins University School of Medicine, Baltimore, Maryland, USA</aff>
<aff id="A23"><label>23</label>
Medical College of Wisconsin, Milwaukee, Wisconsin USA</aff>
<aff id="A24"><label>24</label>
Department of Neurology, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA</aff>
<aff id="A25"><label>25</label>
Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY, USA</aff>
<aff id="A26"><label>26</label>
Center for Human Genetics, College of Physicians and Surgeons, Columbia University, New York, NY, USA</aff>
<aff id="A27"><label>27</label>
Department of Psychiatry, Columbia University Medical Center, NYC, NY, USA</aff>
<author-notes><corresp id="FN1">Corresponding author: Karen Marder, MD, MPH, 622 West 168<sup>th</sup>
Street, NYC, NY 10032, USA. Phone: 212-305-9194, Fax: 212-305-2526, <email>ksm1@columbia.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>22</day>
<month>2</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="ppub"><month>12</month>
<year>2009</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>1</day>
<month>12</month>
<year>2010</year>
</pub-date>
<volume>66</volume>
<issue>12</issue>
<fpage>1517</fpage>
<lpage>1522</lpage>
<abstract><sec id="S1"><title>Objective</title>
<p id="P1">To determine the motor phenotype of <italic>LRRK2</italic>
G2019S mutation carriers</p>
</sec>
<sec id="S2"><title>Background</title>
<p id="P2"><italic>LRRK2</italic>
mutation carriers were previously reported to manifest the tremor-dominant (TD) motor phenotype, which has been associated with slower motor progression and less cognitive impairment compared to the postural instability gait difficulty (PIGD) phenotype.</p>
</sec>
<sec id="S3"><title>Design</title>
<p id="P3">Cross sectional observational study</p>
</sec>
<sec id="S4"><title>Setting</title>
<p id="P4">13 movement disorders centers</p>
</sec>
<sec id="S5"><title>Participants</title>
<p id="P5">925 Early Onset Parkinson Disease (EOPD) cases defined as age at onset (AAO) ≤50.</p>
</sec>
<sec id="S6"><title>Main Outcome Measures</title>
<p id="P6"><italic>LRRK2</italic>
mutation status and PD motor phenotype: TD or PIGD</p>
</sec>
<sec sec-type="methods" id="S7"><title>Methods</title>
<p id="P7">Demographic information, family history of PD (FHPD), and the Unified Parkinson Disease Rating Scale (UPDRS) were collected on all participants. DNA samples were genotyped for <italic>LRRK2</italic>
mutations (G2019S, I2020T, R1441C and Y1699C). Logistic regression was used to examine associations of G2019S mutation status with motor phenotype adjusting for disease duration, Ashkenazi Jewish (AJ) ancestry, levodopa dose, and FHPD.</p>
</sec>
<sec id="S8"><title>Results</title>
<p id="P8">34 cases (3.7%) (14 previously reported) were G2019S carriers. No other mutations were found. Carriers were more likely to be AJ (55.9% vs. 11.9% p<0.001), but did not significantly differ in any other demographic or disease characteristics. Carriers had a lower tremor score (p=0.026) and were more likely to have a PIGD phenotype (92.3% vs. 58.9% p=0.003). The association of the G2019S mutation with PIGD phenotype remained after controlling for disease duration and AJ (OR= 17.7, p< 0.001).</p>
</sec>
<sec id="S9"><title>Conclusion</title>
<p id="P9">EOPD G2019S <italic>LRRK2</italic>
carriers are more likely to manifest the PIGD phenotype, which may have implications for disease course.</p>
</sec>
</abstract>
<contract-num rid="NS1">R01 NS036630-09
||NS</contract-num>
<contract-sponsor id="NS1">National Institute of Neurological Disorders and Stroke : NINDS</contract-sponsor>
</article-meta>
</front>
</pmc>
</record>
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