LRRK2 gene in parkinson disease : Mutation analysis and case control association study
Identifieur interne : 000787 ( PascalFrancis/Checkpoint ); précédent : 000786; suivant : 000788LRRK2 gene in parkinson disease : Mutation analysis and case control association study
Auteurs : C. Paisan-Ruiz [États-Unis, Espagne] ; A. E. Lang [Canada] ; T. Kawarai [Canada] ; C. Sato [Canada] ; S. Salehi-Rad [Canada] ; G. K. Fisman [Canada] ; T. Al-Khairallah [Canada] ; P. St George-Hyslop [Canada] ; A. Singleton [États-Unis] ; E. Rogaeva [Canada]Source :
- Neurology [ 0028-3878 ] ; 2005.
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English descriptors
Abstract
Background: In addition to the four well-confirmed genes linked to early-onset Parkinson disease (PD) (SNCA, PARKIN, DJ-1, and PINK1), mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have recently been identified in families with autosomal dominant late-onset PD. Objective: To perform mutation analysis of LRRK2 in probands of families showing dominant inheritance of PD and to conduct a case control association study to test the hypothesis that common coding variations might be associated with increased susceptibility to PD. Methods: All 51 LRRK2 coding exons were sequenced in 23 probands and the mutation frequencies were evaluated in 180 neurologically normal control subjects. For the association study the authors genotyped four coding LRRK2 polymorphisms in 250 normal control subjects and 121 patients with PD (predominantly white patients of Canadian origin), 84% of whom had age at onset before 50 years and 42% had a positive family history. Results: The authors identified three probands with heterozygous LRRK2 mutations: two of them have the known G2019S substitution and one proband has a novel I1371V substitution. Mutation analysis of a large family demonstrated complete segregation of the G2019S with PD. However, there was no association between PD and any of the four polymorphisms at the allelic or genotypic levels (p > 0.17). Furthermore, the authors did not detect a modifying effect for any genotype or of APOE genotypes upon the age at onset in the PD group (p > 0.20). Conclusions: The results support the prior suggestion that LRRK2 mutations cause PD. The disease in the families reported here presents a phenotype indistinguishable from typical PD. All three families demonstrate a very variable age at onset that is not explained by APOE genotypes. The common coding variations in the LRRK2 gene neither constitute strong PD risk factors nor modify the age at onset; however, the possibility of a modest risk effect remains to be assessed in large datasets.
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National Institute on Aging, National Institutes of Health, Porter Neuroscience Research Center</s1><s2>Bethesda, MD</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Bethesda, MD</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Unitat de Genètica Molecular, Departament de Genòmica i Proteomica, Institut de Biomedicina de València-CSIC</s1><s2>València</s2><s3>ESP</s3><sZ>1 aut.</sZ></inist:fA14><country>Espagne</country><wicri:noRegion>València</wicri:noRegion></affiliation></author><author><name sortKey="Lang, A E" sort="Lang, A E" uniqKey="Lang A" first="A. E." last="Lang">A. E. 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Sato</name><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Centre for Research in Neurodegenerative Diseases, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Salehi Rad, S" sort="Salehi Rad, S" uniqKey="Salehi Rad S" first="S." last="Salehi-Rad">S. Salehi-Rad</name><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Centre for Research in Neurodegenerative Diseases, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Fisman, G K" sort="Fisman, G K" uniqKey="Fisman G" first="G. K." last="Fisman">G. K. Fisman</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Toronto Western Hospital Research Institute, Movement Disorders Centre, Toronto Western Hospital</s1><s3>CAN</s3><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto Western Hospital Research Institute, Movement Disorders Centre, Toronto Western Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Al Khairallah, T" sort="Al Khairallah, T" uniqKey="Al Khairallah T" first="T." last="Al-Khairallah">T. Al-Khairallah</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Toronto Western Hospital Research Institute, Movement Disorders Centre, Toronto Western Hospital</s1><s3>CAN</s3><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto Western Hospital Research Institute, Movement Disorders Centre, Toronto Western Hospital</wicri:noRegion></affiliation></author><author><name sortKey="St George Hyslop, P" sort="St George Hyslop, P" uniqKey="St George Hyslop P" first="P." last="St George-Hyslop">P. St George-Hyslop</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Toronto Western Hospital Research Institute, Movement Disorders Centre, Toronto Western Hospital</s1><s3>CAN</s3><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto Western Hospital Research Institute, Movement Disorders Centre, Toronto Western Hospital</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Department of Medicine, Division of Neurology, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Singleton, A" sort="Singleton, A" uniqKey="Singleton A" first="A." last="Singleton">A. Singleton</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Molecular Genetics Unit. National Institute on Aging, National Institutes of Health, Porter Neuroscience Research Center</s1><s2>Bethesda, MD</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Bethesda, MD</wicri:noRegion></affiliation></author><author><name sortKey="Rogaeva, E" sort="Rogaeva, E" uniqKey="Rogaeva E" first="E." last="Rogaeva">E. Rogaeva</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Department of Medicine, Division of Neurology, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">05-0428988</idno><date when="2005">2005</date><idno type="stanalyst">PASCAL 05-0428988 INIST</idno><idno type="RBID">Pascal:05-0428988</idno><idno type="wicri:Area/PascalFrancis/Corpus">000887</idno><idno type="wicri:Area/PascalFrancis/Curation">000436</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000787</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000787</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">LRRK2 gene in parkinson disease : Mutation analysis and case control association study</title><author><name sortKey="Paisan Ruiz, C" sort="Paisan Ruiz, C" uniqKey="Paisan Ruiz C" first="C." last="Paisan-Ruiz">C. Paisan-Ruiz</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Molecular Genetics Unit. National Institute on Aging, National Institutes of Health, Porter Neuroscience Research Center</s1><s2>Bethesda, MD</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Bethesda, MD</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Unitat de Genètica Molecular, Departament de Genòmica i Proteomica, Institut de Biomedicina de València-CSIC</s1><s2>València</s2><s3>ESP</s3><sZ>1 aut.</sZ></inist:fA14><country>Espagne</country><wicri:noRegion>València</wicri:noRegion></affiliation></author><author><name sortKey="Lang, A E" sort="Lang, A E" uniqKey="Lang A" first="A. E." last="Lang">A. E. Lang</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Toronto Western Hospital Research Institute, Movement Disorders Centre, Toronto Western Hospital</s1><s3>CAN</s3><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto Western Hospital Research Institute, Movement Disorders Centre, Toronto Western Hospital</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Department of Medicine, Division of Neurology, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Kawarai, T" sort="Kawarai, T" uniqKey="Kawarai T" first="T." last="Kawarai">T. Kawarai</name><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Centre for Research in Neurodegenerative Diseases, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Sato, C" sort="Sato, C" uniqKey="Sato C" first="C." last="Sato">C. Sato</name><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Centre for Research in Neurodegenerative Diseases, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Salehi Rad, S" sort="Salehi Rad, S" uniqKey="Salehi Rad S" first="S." last="Salehi-Rad">S. Salehi-Rad</name><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Centre for Research in Neurodegenerative Diseases, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Fisman, G K" sort="Fisman, G K" uniqKey="Fisman G" first="G. K." last="Fisman">G. K. Fisman</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Toronto Western Hospital Research Institute, Movement Disorders Centre, Toronto Western Hospital</s1><s3>CAN</s3><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto Western Hospital Research Institute, Movement Disorders Centre, Toronto Western Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Al Khairallah, T" sort="Al Khairallah, T" uniqKey="Al Khairallah T" first="T." last="Al-Khairallah">T. Al-Khairallah</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Toronto Western Hospital Research Institute, Movement Disorders Centre, Toronto Western Hospital</s1><s3>CAN</s3><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto Western Hospital Research Institute, Movement Disorders Centre, Toronto Western Hospital</wicri:noRegion></affiliation></author><author><name sortKey="St George Hyslop, P" sort="St George Hyslop, P" uniqKey="St George Hyslop P" first="P." last="St George-Hyslop">P. St George-Hyslop</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Toronto Western Hospital Research Institute, Movement Disorders Centre, Toronto Western Hospital</s1><s3>CAN</s3><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto Western Hospital Research Institute, Movement Disorders Centre, Toronto Western Hospital</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Department of Medicine, Division of Neurology, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Singleton, A" sort="Singleton, A" uniqKey="Singleton A" first="A." last="Singleton">A. Singleton</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Molecular Genetics Unit. National Institute on Aging, National Institutes of Health, Porter Neuroscience Research Center</s1><s2>Bethesda, MD</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Bethesda, MD</wicri:noRegion></affiliation></author><author><name sortKey="Rogaeva, E" sort="Rogaeva, E" uniqKey="Rogaeva E" first="E." last="Rogaeva">E. Rogaeva</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Department of Medicine, Division of Neurology, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author></analytic><series><title level="j" type="main">Neurology</title><title level="j" type="abbreviated">Neurology</title><idno type="ISSN">0028-3878</idno><imprint><date when="2005">2005</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Neurology</title><title level="j" type="abbreviated">Neurology</title><idno type="ISSN">0028-3878</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Case control study</term><term>Mutation</term><term>Nervous system diseases</term><term>Parkinson disease</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Système nerveux pathologie</term><term>Parkinson maladie</term><term>Mutation</term><term>Etude cas témoin</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background: In addition to the four well-confirmed genes linked to early-onset Parkinson disease (PD) (SNCA, PARKIN, DJ-1, and PINK1), mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have recently been identified in families with autosomal dominant late-onset PD. Objective: To perform mutation analysis of LRRK2 in probands of families showing dominant inheritance of PD and to conduct a case control association study to test the hypothesis that common coding variations might be associated with increased susceptibility to PD. Methods: All 51 LRRK2 coding exons were sequenced in 23 probands and the mutation frequencies were evaluated in 180 neurologically normal control subjects. For the association study the authors genotyped four coding LRRK2 polymorphisms in 250 normal control subjects and 121 patients with PD (predominantly white patients of Canadian origin), 84% of whom had age at onset before 50 years and 42% had a positive family history. Results: The authors identified three probands with heterozygous LRRK2 mutations: two of them have the known G2019S substitution and one proband has a novel I1371V substitution. Mutation analysis of a large family demonstrated complete segregation of the G2019S with PD. However, there was no association between PD and any of the four polymorphisms at the allelic or genotypic levels (p > 0.17). Furthermore, the authors did not detect a modifying effect for any genotype or of APOE genotypes upon the age at onset in the PD group (p > 0.20). Conclusions: The results support the prior suggestion that LRRK2 mutations cause PD. The disease in the families reported here presents a phenotype indistinguishable from typical PD. All three families demonstrate a very variable age at onset that is not explained by APOE genotypes. The common coding variations in the LRRK2 gene neither constitute strong PD risk factors nor modify the age at onset; however, the possibility of a modest risk effect remains to be assessed in large datasets.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0028-3878</s0></fA01><fA02 i1="01"><s0>NEURAI</s0></fA02><fA03 i2="1"><s0>Neurology</s0></fA03><fA05><s2>65</s2></fA05><fA06><s2>5</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>LRRK2 gene in parkinson disease : Mutation analysis and case control association study</s1></fA08><fA11 i1="01" i2="1"><s1>PAISAN-RUIZ (C.)</s1></fA11><fA11 i1="02" i2="1"><s1>LANG (A. E.)</s1></fA11><fA11 i1="03" i2="1"><s1>KAWARAI (T.)</s1></fA11><fA11 i1="04" i2="1"><s1>SATO (C.)</s1></fA11><fA11 i1="05" i2="1"><s1>SALEHI-RAD (S.)</s1></fA11><fA11 i1="06" i2="1"><s1>FISMAN (G. K.)</s1></fA11><fA11 i1="07" i2="1"><s1>AL-KHAIRALLAH (T.)</s1></fA11><fA11 i1="08" i2="1"><s1>ST GEORGE-HYSLOP (P.)</s1></fA11><fA11 i1="09" i2="1"><s1>SINGLETON (A.)</s1></fA11><fA11 i1="10" i2="1"><s1>ROGAEVA (E.)</s1></fA11><fA14 i1="01"><s1>Molecular Genetics Unit. National Institute on Aging, National Institutes of Health, Porter Neuroscience Research Center</s1><s2>Bethesda, MD</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>9 aut.</sZ></fA14><fA14 i1="02"><s1>Unitat de Genètica Molecular, Departament de Genòmica i Proteomica, Institut de Biomedicina de València-CSIC</s1><s2>València</s2><s3>ESP</s3><sZ>1 aut.</sZ></fA14><fA14 i1="03"><s1>Toronto Western Hospital Research Institute, Movement Disorders Centre, Toronto Western Hospital</s1><s3>CAN</s3><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></fA14><fA14 i1="04"><s1>Department of Medicine, Division of Neurology, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></fA14><fA14 i1="05"><s1>Centre for Research in Neurodegenerative Diseases, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></fA14><fA20><s1>696-700</s1></fA20><fA21><s1>2005</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>6345</s2><s5>354000131690740080</s5></fA43><fA44><s0>0000</s0><s1>© 2005 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>23 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>05-0428988</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Neurology</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>Background: In addition to the four well-confirmed genes linked to early-onset Parkinson disease (PD) (SNCA, PARKIN, DJ-1, and PINK1), mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have recently been identified in families with autosomal dominant late-onset PD. Objective: To perform mutation analysis of LRRK2 in probands of families showing dominant inheritance of PD and to conduct a case control association study to test the hypothesis that common coding variations might be associated with increased susceptibility to PD. Methods: All 51 LRRK2 coding exons were sequenced in 23 probands and the mutation frequencies were evaluated in 180 neurologically normal control subjects. For the association study the authors genotyped four coding LRRK2 polymorphisms in 250 normal control subjects and 121 patients with PD (predominantly white patients of Canadian origin), 84% of whom had age at onset before 50 years and 42% had a positive family history. Results: The authors identified three probands with heterozygous LRRK2 mutations: two of them have the known G2019S substitution and one proband has a novel I1371V substitution. Mutation analysis of a large family demonstrated complete segregation of the G2019S with PD. However, there was no association between PD and any of the four polymorphisms at the allelic or genotypic levels (p > 0.17). Furthermore, the authors did not detect a modifying effect for any genotype or of APOE genotypes upon the age at onset in the PD group (p > 0.20). Conclusions: The results support the prior suggestion that LRRK2 mutations cause PD. The disease in the families reported here presents a phenotype indistinguishable from typical PD. All three families demonstrate a very variable age at onset that is not explained by APOE genotypes. The common coding variations in the LRRK2 gene neither constitute strong PD risk factors nor modify the age at onset; however, the possibility of a modest risk effect remains to be assessed in large datasets.</s0></fC01><fC02 i1="01" i2="X"><s0>002B17</s0></fC02><fC02 i1="02" i2="X"><s0>002B17G</s0></fC02><fC02 i1="03" i2="X"><s0>002B17E</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Système nerveux pathologie</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Nervous system diseases</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Sistema nervioso patología</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Parkinson maladie</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Parkinson disease</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Parkinson enfermedad</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Mutation</s0><s5>09</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Mutation</s0><s5>09</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Mutación</s0><s5>09</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Etude cas témoin</s0><s5>10</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Case control study</s0><s5>10</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Estudio caso control</s0><s5>10</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Encéphale pathologie</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>Extrapyramidal syndrome</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>Système nerveux central pathologie</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><fN21><s1>297</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist><affiliations><list><country><li>Canada</li><li>Espagne</li><li>États-Unis</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="États-Unis"><noRegion><name sortKey="Paisan Ruiz, C" sort="Paisan Ruiz, C" uniqKey="Paisan Ruiz C" first="C." last="Paisan-Ruiz">C. Paisan-Ruiz</name></noRegion><name sortKey="Singleton, A" sort="Singleton, A" uniqKey="Singleton A" first="A." last="Singleton">A. Singleton</name></country><country name="Espagne"><noRegion><name sortKey="Paisan Ruiz, C" sort="Paisan Ruiz, C" uniqKey="Paisan Ruiz C" first="C." last="Paisan-Ruiz">C. Paisan-Ruiz</name></noRegion></country><country name="Canada"><noRegion><name sortKey="Lang, A E" sort="Lang, A E" uniqKey="Lang A" first="A. E." last="Lang">A. E. Lang</name></noRegion><name sortKey="Al Khairallah, T" sort="Al Khairallah, T" uniqKey="Al Khairallah T" first="T." last="Al-Khairallah">T. Al-Khairallah</name><name sortKey="Fisman, G K" sort="Fisman, G K" uniqKey="Fisman G" first="G. K." last="Fisman">G. K. Fisman</name><name sortKey="Kawarai, T" sort="Kawarai, T" uniqKey="Kawarai T" first="T." last="Kawarai">T. Kawarai</name><name sortKey="Lang, A E" sort="Lang, A E" uniqKey="Lang A" first="A. E." last="Lang">A. E. Lang</name><name sortKey="Rogaeva, E" sort="Rogaeva, E" uniqKey="Rogaeva E" first="E." last="Rogaeva">E. Rogaeva</name><name sortKey="Salehi Rad, S" sort="Salehi Rad, S" uniqKey="Salehi Rad S" first="S." last="Salehi-Rad">S. Salehi-Rad</name><name sortKey="Sato, C" sort="Sato, C" uniqKey="Sato C" first="C." last="Sato">C. Sato</name><name sortKey="St George Hyslop, P" sort="St George Hyslop, P" uniqKey="St George Hyslop P" first="P." last="St George-Hyslop">P. St George-Hyslop</name><name sortKey="St George Hyslop, P" sort="St George Hyslop, P" uniqKey="St George Hyslop P" first="P." last="St George-Hyslop">P. St George-Hyslop</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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