SNCA locus duplication carriers: from genetics to Parkinson disease phenotypes
Identifieur interne : 001C24 ( Istex/Corpus ); précédent : 001C23; suivant : 001C25SNCA locus duplication carriers: from genetics to Parkinson disease phenotypes
Auteurs : Eugénie Mutez ; Frédéric Leprêtre ; Emilie Le Rhun ; Lydie Larvor ; Aurélie Duflot ; Vincent Mouroux ; Jean-Pierre Kerckaert ; Martin Figeac ; Kathy Dujardin ; Alain Destée ; Marie-Christine Chartier-HarlinSource :
- Human Mutation [ 1059-7794 ] ; 2011-04.
English descriptors
- KwdEn :
Abstract
Genomic multiplication of the alpha‐synuclein gene (SNCA) locus is one cause of familial Parkinson disease (PD). We performed detailed genomic, SNCA expression level, clinical, neuropsychological and functional imaging analyses of a parkinsonian kindred with a known duplication of the SNCA locus. We demonstrated that the duplication spanned 4.928 Mb (encompassing 31 known and putative genes) and was the largest to have been described at this locus. The presence of several repetitive long interspersed nuclear elements (LINEs) flanking the potential break area suggested that the duplication resulted from a genomic recombination between LINEs. We sequenced the break junction and confirmed the involvement of L1PA2 and L1PA4 in a non‐allelic, homologous recombination. An analysis of mRNA levels in immortalized lymphoblastoid cells and peripheral blood mononuclear cells showed SNCA overexpression in subjects with the duplication, as well as overexpression of 13 other genes highlighting the usefulness of such cell models to study this duplication. Interestingly, abnormal tracer uptake in DaTSCAN® imaging correlated with the severity of the clinical symptoms. Our detailed genomic analysis and clinical exploration enabled us to specify the genotype‐phenotype relationship, identify a case of presymptomatic PD and gain insight into the role of LINEs in SNCA locus duplication. © 2011 Wiley‐Liss, Inc.
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DOI: 10.1002/humu.21459
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ISTEX:243F2079A57EA35B36E0946D26003F3E82592C16Le document en format XML
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uniqKey="Lepretre F" first="Frédéric" last="Leprêtre">Frédéric Leprêtre</name><affiliation><mods:affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Univ Lille Nord de France, Lille, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Functional Genomic Platform, UDSL, IRCL, Lille, France</mods:affiliation></affiliation></author><author><name sortKey="Le Rhun, Emilie" sort="Le Rhun, Emilie" uniqKey="Le Rhun E" first="Emilie" last="Le Rhun">Emilie Le Rhun</name><affiliation><mods:affiliation>Movement Disorders Unit, Lille University Hospital, Lille, France</mods:affiliation></affiliation></author><author><name sortKey="Larvor, Lydie" sort="Larvor, Lydie" uniqKey="Larvor L" first="Lydie" last="Larvor">Lydie Larvor</name><affiliation><mods:affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Univ Lille Nord de France, Lille, France</mods:affiliation></affiliation></author><author><name sortKey="Duflot, Aurelie" sort="Duflot, Aurelie" uniqKey="Duflot A" first="Aurélie" last="Duflot">Aurélie Duflot</name><affiliation><mods:affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Univ Lille Nord de France, Lille, France</mods:affiliation></affiliation></author><author><name sortKey="Mouroux, Vincent" sort="Mouroux, Vincent" uniqKey="Mouroux V" first="Vincent" last="Mouroux">Vincent Mouroux</name><affiliation><mods:affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Univ Lille Nord de France, Lille, France</mods:affiliation></affiliation></author><author><name sortKey="Kerckaert, Jean Ierre" sort="Kerckaert, Jean Ierre" uniqKey="Kerckaert J" first="Jean-Pierre" last="Kerckaert">Jean-Pierre Kerckaert</name><affiliation><mods:affiliation>Univ Lille Nord de France, Lille, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Functional Genomic Platform, UDSL, IRCL, Lille, France</mods:affiliation></affiliation></author><author><name sortKey="Figeac, Martin" sort="Figeac, Martin" uniqKey="Figeac M" first="Martin" last="Figeac">Martin Figeac</name><affiliation><mods:affiliation>Univ Lille Nord de France, Lille, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Functional Genomic Platform, UDSL, IRCL, Lille, France</mods:affiliation></affiliation></author><author><name sortKey="Dujardin, Kathy" sort="Dujardin, Kathy" uniqKey="Dujardin K" first="Kathy" last="Dujardin">Kathy Dujardin</name><affiliation><mods:affiliation>Univ Lille Nord de France, Lille, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Movement Disorders Unit, Lille University Hospital, Lille, France</mods:affiliation></affiliation></author><author><name sortKey="Destee, Alain" sort="Destee, Alain" uniqKey="Destee A" first="Alain" last="Destée">Alain Destée</name><affiliation><mods:affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Univ Lille Nord de France, Lille, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Movement Disorders Unit, Lille University Hospital, Lille, France</mods:affiliation></affiliation></author><author><name sortKey="Chartier Arlin, Marie Hristine" sort="Chartier Arlin, Marie Hristine" uniqKey="Chartier Arlin M" first="Marie-Christine" last="Chartier-Harlin">Marie-Christine Chartier-Harlin</name><affiliation><mods:affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Univ Lille Nord de France, Lille, France</mods:affiliation></affiliation><affiliation><mods:affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Place de Verdun, 59045 Lille Cedex, France</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Mutation</title><title level="j" type="abbrev">Hum. Mutat.</title><idno type="ISSN">1059-7794</idno><idno type="eISSN">1098-1004</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-04">2011-04</date><biblScope unit="volume">32</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="E2079">E2079</biblScope><biblScope unit="page" to="E2090">E2090</biblScope></imprint><idno type="ISSN">1059-7794</idno></series><idno type="istex">243F2079A57EA35B36E0946D26003F3E82592C16</idno><idno type="DOI">10.1002/humu.21459</idno><idno type="ArticleID">HUMU21459</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1059-7794</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Parkinson</term><term>SNCA</term><term>alpha‐synuclein</term><term>duplication</term><term>overexpression</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Genomic multiplication of the alpha‐synuclein gene (SNCA) locus is one cause of familial Parkinson disease (PD). We performed detailed genomic, SNCA expression level, clinical, neuropsychological and functional imaging analyses of a parkinsonian kindred with a known duplication of the SNCA locus. We demonstrated that the duplication spanned 4.928 Mb (encompassing 31 known and putative genes) and was the largest to have been described at this locus. The presence of several repetitive long interspersed nuclear elements (LINEs) flanking the potential break area suggested that the duplication resulted from a genomic recombination between LINEs. We sequenced the break junction and confirmed the involvement of L1PA2 and L1PA4 in a non‐allelic, homologous recombination. An analysis of mRNA levels in immortalized lymphoblastoid cells and peripheral blood mononuclear cells showed SNCA overexpression in subjects with the duplication, as well as overexpression of 13 other genes highlighting the usefulness of such cell models to study this duplication. Interestingly, abnormal tracer uptake in DaTSCAN® imaging correlated with the severity of the clinical symptoms. Our detailed genomic analysis and clinical exploration enabled us to specify the genotype‐phenotype relationship, identify a case of presymptomatic PD and gain insight into the role of LINEs in SNCA locus duplication. © 2011 Wiley‐Liss, Inc.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Eugénie Mutez</name><affiliations><json:string>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</json:string><json:string>Univ Lille Nord de France, Lille, France</json:string><json:string>Movement Disorders Unit, Lille University Hospital, Lille, France</json:string></affiliations></json:item><json:item><name>Frédéric Leprêtre</name><affiliations><json:string>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</json:string><json:string>Univ Lille Nord de France, Lille, France</json:string><json:string>Functional Genomic Platform, UDSL, IRCL, Lille, France</json:string></affiliations></json:item><json:item><name>Emilie Le Rhun</name><affiliations><json:string>Movement Disorders Unit, Lille University Hospital, Lille, France</json:string></affiliations></json:item><json:item><name>Lydie Larvor</name><affiliations><json:string>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</json:string><json:string>Univ Lille Nord de France, Lille, France</json:string></affiliations></json:item><json:item><name>Aurélie Duflot</name><affiliations><json:string>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</json:string><json:string>Univ Lille Nord de France, Lille, France</json:string></affiliations></json:item><json:item><name>Vincent Mouroux</name><affiliations><json:string>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</json:string><json:string>Univ Lille Nord de France, Lille, France</json:string></affiliations></json:item><json:item><name>Jean‐Pierre Kerckaert</name><affiliations><json:string>Univ Lille Nord de France, Lille, France</json:string><json:string>Functional Genomic Platform, UDSL, IRCL, Lille, France</json:string></affiliations></json:item><json:item><name>Martin Figeac</name><affiliations><json:string>Univ Lille Nord de France, Lille, France</json:string><json:string>Functional Genomic Platform, UDSL, IRCL, Lille, France</json:string></affiliations></json:item><json:item><name>Kathy Dujardin</name><affiliations><json:string>Univ Lille Nord de France, Lille, France</json:string><json:string>Movement Disorders Unit, Lille University Hospital, Lille, France</json:string></affiliations></json:item><json:item><name>Alain Destée</name><affiliations><json:string>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</json:string><json:string>Univ Lille Nord de France, Lille, France</json:string><json:string>Movement Disorders Unit, Lille University Hospital, Lille, France</json:string></affiliations></json:item><json:item><name>Marie‐Christine Chartier‐Harlin</name><affiliations><json:string>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</json:string><json:string>Univ Lille Nord de France, Lille, France</json:string><json:string>UMR 837 INSERM, Team 6, JParc, IRCL, Place de Verdun, 59045 Lille Cedex, France</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Parkinson</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>alpha‐synuclein</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>SNCA</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>duplication</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>overexpression</value></json:item></subject><articleId><json:string>HUMU21459</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>shortCommunication</json:string></originalGenre><abstract>Genomic multiplication of the alpha‐synuclein gene (SNCA) locus is one cause of familial Parkinson disease (PD). We performed detailed genomic, SNCA expression level, clinical, neuropsychological and functional imaging analyses of a parkinsonian kindred with a known duplication of the SNCA locus. We demonstrated that the duplication spanned 4.928 Mb (encompassing 31 known and putative genes) and was the largest to have been described at this locus. The presence of several repetitive long interspersed nuclear elements (LINEs) flanking the potential break area suggested that the duplication resulted from a genomic recombination between LINEs. We sequenced the break junction and confirmed the involvement of L1PA2 and L1PA4 in a non‐allelic, homologous recombination. An analysis of mRNA levels in immortalized lymphoblastoid cells and peripheral blood mononuclear cells showed SNCA overexpression in subjects with the duplication, as well as overexpression of 13 other genes highlighting the usefulness of such cell models to study this duplication. Interestingly, abnormal tracer uptake in DaTSCAN® imaging correlated with the severity of the clinical symptoms. Our detailed genomic analysis and clinical exploration enabled us to specify the genotype‐phenotype relationship, identify a case of presymptomatic PD and gain insight into the role of LINEs in SNCA locus duplication. © 2011 Wiley‐Liss, Inc.</abstract><qualityIndicators><score>7.924</score><pdfVersion>1.4</pdfVersion><pdfPageSize>612 x 792 pts (letter)</pdfPageSize><refBibsNative>false</refBibsNative><abstractCharCount>1411</abstractCharCount><pdfWordCount>5751</pdfWordCount><pdfCharCount>37130</pdfCharCount><pdfPageCount>12</pdfPageCount><abstractWordCount>202</abstractWordCount></qualityIndicators><title>SNCA locus duplication carriers: from genetics to Parkinson disease phenotypes</title><refBibs><json:item><author><json:item><name>J Cho</name></json:item><json:item><name>Bs Jeon</name></json:item></author><host><volume>70</volume><pages><last>49</last><first>43</first></pages><author></author><title>Neurology</title><publicationDate>2008</publicationDate></host><title>alpha- Synuclein gene duplication is present in sporadic Parkinson disease</title><publicationDate>2008</publicationDate></json:item><json:item><author><json:item><name>Dv Babashok</name></json:item><json:item><name>Hh Kazazian</name></json:item></author><host><pages><last>539</last><first>527</first></pages><author></author><title>Progress in understanding the biology of the human mutagen LINE-1</title><publicationDate>2007</publicationDate></host><publicationDate>2007</publicationDate></json:item><json:item><author><json:item><name>Vp Belancio</name></json:item><json:item><name>Pl Deininger</name></json:item><json:item><name>Am Roy-Engel</name></json:item></author><host><volume>1</volume><pages><first>97</first></pages><author></author><title>Genome Med</title><publicationDate>2009</publicationDate></host><title>LINE dancing in the human genome: transposable elements and disease</title><publicationDate>2009</publicationDate></json:item><json:item><author><json:item><name>Mc Chartier-Harlin</name></json:item><json:item><name>J Kachergus</name></json:item><json:item><name>C Roumier</name></json:item><json:item><name>V Mouroux</name></json:item><json:item><name>X Douay</name></json:item><json:item><name>S Lincoln</name></json:item><json:item><name>C Levecque</name></json:item><json:item><name>L Larvor</name></json:item><json:item><name>J Andrieux</name></json:item><json:item><name>M Hulihan</name></json:item><json:item><name>N Waucquier</name></json:item><json:item><name>L Defebvre</name></json:item><json:item><name>P Amouyel</name></json:item><json:item><name>M Farrer</name></json:item><json:item><name>A Destée</name></json:item></author><host><volume>364</volume><pages><last>1169</last><first>1167</first></pages><author></author><title>Lancet</title><publicationDate>2004</publicationDate></host><title>Alpha-synuclein locus duplication causes familial Parkinson's disease</title><publicationDate>2004</publicationDate></json:item><json:item><author><json:item><name>Df Conrad</name></json:item><json:item><name>C Bird</name></json:item><json:item><name>B Blackburne</name></json:item><json:item><name>S Lindsay</name></json:item><json:item><name>L Mamanova</name></json:item><json:item><name>C Lee</name></json:item><json:item><name>Dj Turner</name></json:item><json:item><name>Me Hurles</name></json:item></author><host><volume>42</volume><pages><last>391</last><first>385</first></pages><author></author><title>Nat Genet</title><publicationDate>2010</publicationDate></host><title>Mutation spectrum revealed by breakpoint sequencing of human germline CNVs</title><publicationDate>2010</publicationDate></json:item><json:item><author><json:item><name>K Dujardin</name></json:item><json:item><name>P Krystkowiak</name></json:item><json:item><name>L Defebvre</name></json:item><json:item><name>S Blond</name></json:item><json:item><name>Destée,A </name></json:item></author><host><volume>38</volume><pages><last>1315</last><first>1305</first></pages><author></author><title>Neuropsychologia</title><publicationDate>2000</publicationDate></host><title>A case of severe dysexecutive syndrome consecutive to chronic bilateral pallidal stimulation</title><publicationDate>2000</publicationDate></json:item><json:item><author><json:item><name>M Emre</name></json:item><json:item><name>D Aarsland</name></json:item><json:item><name>R Brown</name></json:item><json:item><name>Dj Burn</name></json:item><json:item><name>C Duyckaerts</name></json:item><json:item><name>Y Mizuno</name></json:item><json:item><name>Ga Broe</name></json:item><json:item><name>J Cummings</name></json:item><json:item><name>Dw Dickson</name></json:item><json:item><name>S Gauthier</name></json:item><json:item><name>J Goldman</name></json:item><json:item><name>C Goetz</name></json:item><json:item><name>A Korczyn</name></json:item><json:item><name>A Lees</name></json:item><json:item><name>R Levy</name></json:item><json:item><name>I Litvan</name></json:item><json:item><name>I Mckeith</name></json:item><json:item><name>W Olanow</name></json:item><json:item><name>W Poewe</name></json:item><json:item><name>N Quinn</name></json:item><json:item><name>C Sampaio</name></json:item><json:item><name>E Tolosa</name></json:item><json:item><name>B Dubois</name></json:item></author><host><volume>22</volume><pages><last>1707</last><first>1689</first></pages><author></author><title>Mov Disord</title><publicationDate>2007</publicationDate></host><title>Clinical diagnostic criteria for dementia associated with Parkinson's disease</title><publicationDate>2007</publicationDate></json:item><json:item><author><json:item><name>P Ibáñez</name></json:item><json:item><name>S Lesage</name></json:item><json:item><name>S Janin</name></json:item><json:item><name>E Lohmann</name></json:item><json:item><name>F Durif</name></json:item><json:item><name>A Destée</name></json:item><json:item><name>Am Bonnet</name></json:item><json:item><name>C Brefel-Courbon</name></json:item><json:item><name>S Heath</name></json:item><json:item><name>D Zelenika</name></json:item><json:item><name>Y Agid</name></json:item><json:item><name>A Dürr</name></json:item><json:item><name>A Brice</name></json:item></author><host><volume>66</volume><pages><last>108</last><first>102</first></pages><author></author><title>Arch Neurol</title><publicationDate>2009</publicationDate></host><title>Alpha-synuclein gene rearrangements in dominantly inherited parkinsonism: frequency, phenotype, and mechanisms</title><publicationDate>2009</publicationDate></json:item><json:item><author><json:item><name>K Inoue</name></json:item><json:item><name>Jr Lupski</name></json:item></author><host><volume>3</volume><pages><last>242</last><first>199</first></pages><author></author><title>Annu Rev Genomics Hum Genet</title><publicationDate>2002</publicationDate></host><title>Molecular mechanisms for genomic disorders</title><publicationDate>2002</publicationDate></json:item><json:item><author><json:item><name>Je Lee</name></json:item><json:item><name>Hy Nam</name></json:item><json:item><name>Sm Shim</name></json:item><json:item><name>Gr Bae</name></json:item><json:item><name>Bg Han</name></json:item><json:item><name>Jp Jeon</name></json:item></author><host><volume>43</volume><pages><last>384</last><first>378</first></pages><author></author><title>Cell Prolif</title><publicationDate>2010</publicationDate></host><title>Expression phenotype changes of EBV-transformed lymphoblastoid cell lines during long-term subculture and its clinical significance</title><publicationDate>2010</publicationDate></json:item><json:item><author><json:item><name>S Lesage</name></json:item><json:item><name>A Brice</name></json:item></author><host><volume>18</volume><pages><last>59</last><first>48</first></pages><author></author><title>Hum Mol Genet</title><publicationDate>2009</publicationDate></host><title>Parkinson's disease: from monogenic forms to genetic susceptibility factors</title><publicationDate>2009</publicationDate></json:item><json:item><author><json:item><name>Tg Lesnick</name></json:item><json:item><name>S Papapetropoulos</name></json:item><json:item><name>Dc Mash</name></json:item><json:item><name>J Ffrench-Mullen</name></json:item><json:item><name>L Shehadeh</name></json:item><json:item><name>M De Andrade</name></json:item><json:item><name>Jr Henley</name></json:item><json:item><name>Wa Rocca</name></json:item><json:item><name>Je Ahlskog</name></json:item><json:item><name>Dm Maraganore</name></json:item></author><host><volume>3</volume><pages><first>98</first></pages><author></author><title>PLoS Genet</title><publicationDate>2007</publicationDate></host><title>A genomic pathway approach to a complex disease: axon guidance and Parkinson disease</title><publicationDate>2007</publicationDate></json:item><json:item><author><json:item><name>Dm Maraganore</name></json:item><json:item><name>M De Andrade</name></json:item><json:item><name>A Elbaz</name></json:item><json:item><name>Mj Farrer</name></json:item><json:item><name>Jp Ioannidis</name></json:item><json:item><name>R Krüger</name></json:item><json:item><name>Wa Rocca</name></json:item><json:item><name>Nk Schneider</name></json:item><json:item><name>Tg Lesnick</name></json:item><json:item><name>Sj Lincoln</name></json:item><json:item><name>Mm Hulihan</name></json:item><json:item><name>Jo Aasly</name></json:item><json:item><name>T Ashizawa</name></json:item><json:item><name>Mc Chartier-Harlin</name></json:item><json:item><name>H Checkoway</name></json:item><json:item><name>C Ferrarese</name></json:item><json:item><name>G Hadjigeorgiou</name></json:item><json:item><name>N Hattori</name></json:item><json:item><name>H Kawakami</name></json:item><json:item><name>Jc Lambert</name></json:item><json:item><name>T Lynch</name></json:item><json:item><name>Gd Mellick</name></json:item><json:item><name>S Papapetropoulos</name></json:item><json:item><name>A Parsian</name></json:item><json:item><name>A Quattrone</name></json:item><json:item><name>O Riess</name></json:item><json:item><name>Ek Tan</name></json:item></author><host><volume>296</volume><pages><last>670</last><first>661</first></pages><author></author><title>Genetic Epidemiology of Parkinson's Disease JAMA</title><publicationDate>2006</publicationDate></host><title>Collaborative analysis of alpha-synuclein gene promoter variability and Parkinson disease</title><publicationDate>2006</publicationDate></json:item><json:item><host><pages><last>1016</last><first>10</first></pages><author><json:item><name>E Mutez</name></json:item><json:item><name>L Larvor</name></json:item><json:item><name>F Leprêtre</name></json:item><json:item><name>V Mouroux</name></json:item><json:item><name>D Hamalek</name></json:item><json:item><name>Jp Kerckaert</name></json:item><json:item><name>J Pérez-Tur</name></json:item><json:item><name>N Waucquier</name></json:item><json:item><name>C Vanbesien-Mailliot</name></json:item><json:item><name>A Duflot</name></json:item><json:item><name>D Devos</name></json:item><json:item><name>L Defebvre</name></json:item><json:item><name>A Kreisler</name></json:item><json:item><name>B Frigard</name></json:item><json:item><name>A Destée</name></json:item><json:item><name>Mc Chartier-Harlin</name></json:item></author><title>Transcriptional profile of Parkinson blood mononuclear cells with LRRK2 mutation</title></host></json:item><json:item><author><json:item><name>K Nishioka</name></json:item><json:item><name>S Hayashi</name></json:item><json:item><name>Mj Farrer</name></json:item><json:item><name>Ab Singleton</name></json:item><json:item><name>H Yoshino</name></json:item><json:item><name>H Imai</name></json:item><json:item><name>T Kitami</name></json:item><json:item><name>K Sato</name></json:item><json:item><name>R Kuroda</name></json:item><json:item><name>H Tomiyama</name></json:item><json:item><name>K Mizoguchi</name></json:item><json:item><name>M Murata</name></json:item><json:item><name>T Toda</name></json:item><json:item><name>I Imoto</name></json:item><json:item><name>J Inazawa</name></json:item><json:item><name>Y Mizuno</name></json:item><json:item><name>N Hattori</name></json:item></author><host><volume>59</volume><pages><last>309</last><first>298</first></pages><author></author><title>Ann Neurol</title><publicationDate>2006</publicationDate></host><title>Clinical heterogeneity of α-synuclein gene duplication in Parkinson's disease</title><publicationDate>2006</publicationDate></json:item><json:item><author><json:item><name>K Nishioka</name></json:item><json:item><name>Oa Ross</name></json:item><json:item><name>K Ishii</name></json:item><json:item><name>Jm Kachergus</name></json:item><json:item><name>K Ishiwata</name></json:item><json:item><name>M Kitagawa</name></json:item><json:item><name>S Kono</name></json:item><json:item><name>T Obi</name></json:item><json:item><name>K Mizoguchi</name></json:item><json:item><name>Y Inoue</name></json:item><json:item><name>H Imai</name></json:item><json:item><name>M Takanashi</name></json:item><json:item><name>Y Mizuno</name></json:item><json:item><name>Mj Farrer</name></json:item><json:item><name>N Hattori</name></json:item></author><host><volume>24</volume><pages><last>1819</last><first>1811</first></pages><author></author><title>Mov Disord</title><publicationDate>2009</publicationDate></host><title>Expanding the clinical phenotype of SNCA duplication carriers</title><publicationDate>2009</publicationDate></json:item><json:item><author><json:item><name>T Penzkofer</name></json:item><json:item><name>T Dandekar</name></json:item><json:item><name>T Zemojtel</name></json:item></author><host><volume>33</volume><pages><last>500</last><first>498</first></pages><author></author><title>Nucleic Acids Res</title><publicationDate>2005</publicationDate></host><title>L1base: from functional annotation to prediction of active LINE-1 elements</title><publicationDate>2005</publicationDate></json:item><json:item><author><json:item><name>Mh Polymeropoulos</name></json:item><json:item><name>C Lavedan</name></json:item><json:item><name>E Leroy</name></json:item><json:item><name>Se Ide</name></json:item><json:item><name>A Dehejia</name></json:item><json:item><name>A Dutra</name></json:item><json:item><name>B Pike</name></json:item><json:item><name>H Root</name></json:item><json:item><name>J Rubenstein</name></json:item><json:item><name>R Boyer</name></json:item><json:item><name>Es Stenroos</name></json:item><json:item><name>S Chandrasekharappa</name></json:item><json:item><name>A Athanassiadou</name></json:item><json:item><name>T Papapetropoulos</name></json:item><json:item><name>Wg Johnson</name></json:item><json:item><name>Am Lazzarini</name></json:item><json:item><name>Rc Duvoisin</name></json:item><json:item><name>Di Iorio</name></json:item><json:item><name>G Golbe</name></json:item><json:item><name>Li Nussbaum</name></json:item><json:item><name>Rl </name></json:item></author><host><volume>276</volume><pages><last>2047</last><first>2045</first></pages><author></author><title>Science</title><publicationDate>1997</publicationDate></host><title>Mutation in the alpha-synuclein gene identified in families with Parkinson's disease</title><publicationDate>1997</publicationDate></json:item><json:item><author><json:item><name>Oa Ross</name></json:item><json:item><name>At Braithwaite</name></json:item><json:item><name>Lm Skipper</name></json:item><json:item><name>J Kachergus</name></json:item><json:item><name>Mm Hulihan</name></json:item><json:item><name>Fa Middleton</name></json:item><json:item><name>K Nishioka</name></json:item><json:item><name>J Fuchs</name></json:item><json:item><name>T Gasser</name></json:item><json:item><name>Dm Maraganore</name></json:item><json:item><name>Ch Adler</name></json:item><json:item><name>L Larvor</name></json:item><json:item><name>Mc Chartier-Harlin</name></json:item><json:item><name>C Nilsson</name></json:item><json:item><name>Jw Langston</name></json:item><json:item><name>K Gwinn</name></json:item><json:item><name>N Hattori</name></json:item><json:item><name>Mj Farrer</name></json:item></author><host><volume>63</volume><pages><last>750</last><first>743</first></pages><author></author><title>Ann Neurol</title><publicationDate>2008</publicationDate></host><title>Genomic investigation of α-synuclein multiplication and Parkinsonism</title><publicationDate>2008</publicationDate></json:item><json:item><author><json:item><name>L Rozier</name></json:item><json:item><name>E El-Achkar</name></json:item><json:item><name>F Apiou</name></json:item><json:item><name>M Debatisse</name></json:item></author><host><volume>23</volume><pages><last>6880</last><first>6872</first></pages><author></author><title>Oncogene</title><publicationDate>2004</publicationDate></host><title>Characterization of a conserved aphidicolin-sensitive common fragile site at human 4q22 and mouse 6C1: possible association with an inherited disease and cancer</title><publicationDate>2004</publicationDate></json:item><json:item><author><json:item><name>K Rugbjerg</name></json:item><json:item><name>S Friis</name></json:item><json:item><name>Tl Jørgensen</name></json:item><json:item><name>B Ritz</name></json:item><json:item><name>L Korbo</name></json:item><json:item><name>Jh Olsen</name></json:item></author><host><volume>25</volume><pages><last>2360</last><first>2355</first></pages><author></author><title>Mov Disord</title><publicationDate>2010</publicationDate></host><title>Risk for Parkinson's disease among patients with osteoarthritis: a Danish cohort study</title><publicationDate>2010</publicationDate></json:item><json:item><author><json:item><name>W Satake</name></json:item><json:item><name>Y Nakabayashi</name></json:item><json:item><name>I Mizuta</name></json:item><json:item><name>Y Hirota</name></json:item><json:item><name>C Ito</name></json:item><json:item><name>M Kubo</name></json:item><json:item><name>T Kawaguchi</name></json:item><json:item><name>T Tsunoda</name></json:item><json:item><name>M Watanabe</name></json:item><json:item><name>A Takeda</name></json:item><json:item><name>H Tomiyama</name></json:item><json:item><name>K Nakashima</name></json:item><json:item><name>K Hasegawa</name></json:item><json:item><name>F Obata</name></json:item><json:item><name>T Yoshikawa</name></json:item><json:item><name>H Kawakami</name></json:item><json:item><name>S Sakoda</name></json:item><json:item><name>M Yamamoto</name></json:item><json:item><name>N Hattori</name></json:item><json:item><name>M Murata</name></json:item><json:item><name>Y Nakamura</name></json:item><json:item><name>T Toda</name></json:item></author><host><volume>41</volume><pages><last>1307</last><first>1303</first></pages><author></author><title>Nat Genet</title><publicationDate>2009</publicationDate></host><title>Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease</title><publicationDate>2009</publicationDate></json:item><json:item><author><json:item><name>Cr Scherzer</name></json:item><json:item><name>Ac Eklund</name></json:item><json:item><name>Lj Morse</name></json:item><json:item><name>Z Liao</name></json:item><json:item><name>Jj Locascio</name></json:item><json:item><name>D Fefer</name></json:item><json:item><name>Ma Schwarzschild</name></json:item><json:item><name>Mg Schlossmacher</name></json:item><json:item><name>Ma Hauser</name></json:item><json:item><name>Jm Vance</name></json:item><json:item><name>Lr Sudarsky</name></json:item><json:item><name>Dg Standaert</name></json:item><json:item><name>Jh Growdon</name></json:item><json:item><name>Rv Jensen</name></json:item><json:item><name>Sr Gullans</name></json:item></author><host><volume>104</volume><pages><last>960</last><first>955</first></pages><author></author><title>Proc Natl Acad Sci</title><publicationDate>2007</publicationDate></host><title>Molecular markers of early Parkinson's disease based on gene expression in blood</title><publicationDate>2007</publicationDate></json:item><json:item><author><json:item><name>Td Schmittgen</name></json:item><json:item><name>Kj Livak</name></json:item></author><host><volume>3</volume><pages><last>1108</last><first>1101</first></pages><author></author><title>Nat Protoc</title><publicationDate>2008</publicationDate></host><title>Analyzing real-time PCR data by the comparative C(T) method</title><publicationDate>2008</publicationDate></json:item><json:item><author><json:item><name>Cj Shaw</name></json:item><json:item><name>Jr Lupski</name></json:item></author><host><volume>13</volume><pages><last>64</last><first>57</first></pages><author></author><title>Hum Mol Genet</title><publicationDate>2004</publicationDate></host><title>Implications of human genome architecture for rearrangement-based disorders: the genomic basis of disease</title><publicationDate>2004</publicationDate></json:item><json:item><host><author><json:item><name>J Simón-Sánchez</name></json:item><json:item><name>C Schulte</name></json:item><json:item><name>Jm Bras</name></json:item><json:item><name>M Sharma</name></json:item><json:item><name>Jr Gibbs</name></json:item><json:item><name>D Berg</name></json:item><json:item><name>C Paisan-Ruiz</name></json:item><json:item><name>P Lichtner</name></json:item><json:item><name>Sw Scholz</name></json:item><json:item><name>Dg Hernandez</name></json:item><json:item><name>R Krüger</name></json:item><json:item><name>M Federoff</name></json:item><json:item><name>C Klein</name></json:item><json:item><name>A Goate</name></json:item><json:item><name>J Perlmutter</name></json:item><json:item><name>M Bonin</name></json:item><json:item><name>Ma Nalls</name></json:item></author></host></json:item></refBibs><genre><json:string>brief-communication</json:string></genre><host><volume>32</volume><publisherId><json:string>HUMU</json:string></publisherId><pages><total>12</total><last>E2090</last><first>E2079</first></pages><issn><json:string>1059-7794</json:string></issn><issue>4</issue><subject><json:item><value>Mutation in Brief</value></json:item></subject><genre><json:string>journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1098-1004</json:string></eissn><title>Human Mutation</title><doi><json:string>10.1002/(ISSN)1098-1004</json:string></doi></host><categories><wos><json:string>science</json:string><json:string>genetics & heredity</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>biomedical research</json:string><json:string>genetics & heredity</json:string></scienceMetrix></categories><publicationDate>2011</publicationDate><copyrightDate>2011</copyrightDate><doi><json:string>10.1002/humu.21459</json:string></doi><id>243F2079A57EA35B36E0946D26003F3E82592C16</id><score>0.33643675</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/243F2079A57EA35B36E0946D26003F3E82592C16/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/243F2079A57EA35B36E0946D26003F3E82592C16/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/243F2079A57EA35B36E0946D26003F3E82592C16/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">SNCA locus duplication carriers: from genetics to Parkinson disease phenotypes</title><respStmt><resp>Références bibliographiques récupérées via GROBID</resp><name resp="ISTEX-API">ISTEX-API (INIST-CNRS)</name></respStmt><respStmt><resp>Références bibliographiques récupérées via GROBID</resp><name resp="ISTEX-API">ISTEX-API (INIST-CNRS)</name></respStmt></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>© 2011 Wiley‐Liss, Inc.</p></availability><date>2011</date></publicationStmt><notesStmt><note type="content">*Communicated by Christine Van Broeckhoven</note><note>Univ Lille Nord de France, INSERM, Lille University Hospital, French Ministry of Research - No. PHRC PARKFANORD (2005/1914).;</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">SNCA locus duplication carriers: from genetics to Parkinson disease phenotypes</title><author xml:id="author-1"><persName><forename type="first">Eugénie</forename><surname>Mutez</surname></persName><note type="biography">These authors contributed equally to the study</note><affiliation>These authors contributed equally to the study</affiliation><affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</affiliation><affiliation>Univ Lille Nord de France, Lille, France</affiliation><affiliation>Movement Disorders Unit, Lille University Hospital, Lille, France</affiliation></author><author xml:id="author-2"><persName><forename type="first">Frédéric</forename><surname>Leprêtre</surname></persName><note type="biography">These authors contributed equally to the study</note><affiliation>These authors contributed equally to the study</affiliation><affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</affiliation><affiliation>Univ Lille Nord de France, Lille, France</affiliation><affiliation>Functional Genomic Platform, UDSL, IRCL, Lille, France</affiliation></author><author xml:id="author-3"><persName><forename type="first">Emilie</forename><surname>Le Rhun</surname></persName><note type="biography">These authors contributed equally to the study</note><affiliation>These authors contributed equally to the study</affiliation><affiliation>Movement Disorders Unit, Lille University Hospital, Lille, France</affiliation></author><author xml:id="author-4"><persName><forename type="first">Lydie</forename><surname>Larvor</surname></persName><note type="biography">These authors contributed equally to the study</note><affiliation>These authors contributed equally to the study</affiliation><affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</affiliation><affiliation>Univ Lille Nord de France, Lille, France</affiliation></author><author xml:id="author-5"><persName><forename type="first">Aurélie</forename><surname>Duflot</surname></persName><affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</affiliation><affiliation>Univ Lille Nord de France, Lille, France</affiliation></author><author xml:id="author-6"><persName><forename type="first">Vincent</forename><surname>Mouroux</surname></persName><affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</affiliation><affiliation>Univ Lille Nord de France, Lille, France</affiliation></author><author xml:id="author-7"><persName><forename type="first">Jean‐Pierre</forename><surname>Kerckaert</surname></persName><affiliation>Univ Lille Nord de France, Lille, France</affiliation><affiliation>Functional Genomic Platform, UDSL, IRCL, Lille, France</affiliation></author><author xml:id="author-8"><persName><forename type="first">Martin</forename><surname>Figeac</surname></persName><affiliation>Univ Lille Nord de France, Lille, France</affiliation><affiliation>Functional Genomic Platform, UDSL, IRCL, Lille, France</affiliation></author><author xml:id="author-9"><persName><forename type="first">Kathy</forename><surname>Dujardin</surname></persName><affiliation>Univ Lille Nord de France, Lille, France</affiliation><affiliation>Movement Disorders Unit, Lille University Hospital, Lille, France</affiliation></author><author xml:id="author-10"><persName><forename type="first">Alain</forename><surname>Destée</surname></persName><affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</affiliation><affiliation>Univ Lille Nord de France, Lille, France</affiliation><affiliation>Movement Disorders Unit, Lille University Hospital, Lille, France</affiliation></author><author xml:id="author-11"><persName><forename type="first">Marie‐Christine</forename><surname>Chartier‐Harlin</surname></persName><affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</affiliation><affiliation>Univ Lille Nord de France, Lille, France</affiliation><affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Place de Verdun, 59045 Lille Cedex, France</affiliation></author></analytic><monogr><title level="j">Human Mutation</title><title level="j" type="abbrev">Hum. Mutat.</title><idno type="pISSN">1059-7794</idno><idno type="eISSN">1098-1004</idno><idno type="DOI">10.1002/(ISSN)1098-1004</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-04"></date><biblScope unit="volume">32</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="E2079">E2079</biblScope><biblScope unit="page" to="E2090">E2090</biblScope></imprint></monogr><idno type="istex">243F2079A57EA35B36E0946D26003F3E82592C16</idno><idno type="DOI">10.1002/humu.21459</idno><idno type="ArticleID">HUMU21459</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2011</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Genomic multiplication of the alpha‐synuclein gene (SNCA) locus is one cause of familial Parkinson disease (PD). We performed detailed genomic, SNCA expression level, clinical, neuropsychological and functional imaging analyses of a parkinsonian kindred with a known duplication of the SNCA locus. We demonstrated that the duplication spanned 4.928 Mb (encompassing 31 known and putative genes) and was the largest to have been described at this locus. The presence of several repetitive long interspersed nuclear elements (LINEs) flanking the potential break area suggested that the duplication resulted from a genomic recombination between LINEs. We sequenced the break junction and confirmed the involvement of L1PA2 and L1PA4 in a non‐allelic, homologous recombination. An analysis of mRNA levels in immortalized lymphoblastoid cells and peripheral blood mononuclear cells showed SNCA overexpression in subjects with the duplication, as well as overexpression of 13 other genes highlighting the usefulness of such cell models to study this duplication. Interestingly, abnormal tracer uptake in DaTSCAN® imaging correlated with the severity of the clinical symptoms. Our detailed genomic analysis and clinical exploration enabled us to specify the genotype‐phenotype relationship, identify a case of presymptomatic PD and gain insight into the role of LINEs in SNCA locus duplication. © 2011 Wiley‐Liss, Inc.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>keywords</head><item><term>Parkinson</term></item><item><term>alpha‐synuclein</term></item><item><term>SNCA</term></item><item><term>duplication</term></item><item><term>overexpression</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article-category</head><item><term>Mutation in Brief</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2010-10-18">Received</change><change when="2011-01-12">Registration</change><change when="2011-04">Published</change><change xml:id="refBibs-istex" who="#ISTEX-API" when="2016-12-13">References added</change><change xml:id="refBibs-istex" who="#ISTEX-API" when="2017-02-8">References added</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/243F2079A57EA35B36E0946D26003F3E82592C16/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley component found"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1098-1004</doi><issn type="print">1059-7794</issn><issn type="electronic">1098-1004</issn><idGroup><id type="product" value="HUMU"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="HUMAN MUTATION">Human Mutation</title><title type="short">Hum. Mutat.</title></titleGroup></publicationMeta><publicationMeta level="part" position="40"><doi origin="wiley" registered="yes">10.1002/humu.v32.4</doi><numberingGroup><numbering type="journalVolume" number="32">32</numbering><numbering type="journalIssue">4</numbering></numberingGroup><coverDate startDate="2011-04">April 2011</coverDate></publicationMeta><publicationMeta level="unit" type="shortCommunication" position="22" status="forIssue"><doi origin="wiley" registered="yes">10.1002/humu.21459</doi><idGroup><id type="unit" value="HUMU21459"></id></idGroup><countGroup><count type="pageTotal" number="12"></count></countGroup><titleGroup><title type="articleCategory">Mutation in Brief</title><title type="tocHeading1">Mutations in Brief</title></titleGroup><copyright ownership="publisher">© 2011 Wiley‐Liss, Inc.</copyright><eventGroup><event type="manuscriptReceived" date="2010-10-18"></event><event type="manuscriptAccepted" date="2011-01-12"></event><event type="xmlConverted" 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type="referenceTotal" number="29"></count></countGroup><titleGroup><title type="main" xml:lang="en">SNCA locus duplication carriers: from genetics to Parkinson disease phenotypes<link href="#fn1"></link></title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1 #af2 #af3" noteRef="#fn2"><personName><givenNames>Eugénie</givenNames><familyName>Mutez</familyName></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1 #af2 #af4" noteRef="#fn2"><personName><givenNames>Frédéric</givenNames><familyName>Leprêtre</familyName></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af3" noteRef="#fn2"><personName><givenNames>Emilie</givenNames><familyName>Le Rhun</familyName></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af1 #af2" noteRef="#fn2"><personName><givenNames>Lydie</givenNames><familyName>Larvor</familyName></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af1 #af2"><personName><givenNames>Aurélie</givenNames><familyName>Duflot</familyName></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af1 #af2"><personName><givenNames>Vincent</givenNames><familyName>Mouroux</familyName></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af2 #af4"><personName><givenNames>Jean‐Pierre</givenNames><familyName>Kerckaert</familyName></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af2 #af4"><personName><givenNames>Martin</givenNames><familyName>Figeac</familyName></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af2 #af3"><personName><givenNames>Kathy</givenNames><familyName>Dujardin</familyName></personName></creator><creator xml:id="au10" creatorRole="author" affiliationRef="#af1 #af2 #af3"><personName><givenNames>Alain</givenNames><familyName>Destée</familyName></personName></creator><creator xml:id="au11" creatorRole="author" affiliationRef="#af1 #af2" corresponding="yes"><personName><givenNames>Marie‐Christine</givenNames><familyName>Chartier‐Harlin</familyName></personName><contactDetails><email normalForm="marie-christine.chartier-harlin@inserm.fr">marie‐christine.chartier‐harlin@inserm.fr</email></contactDetails></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="FR" type="organization"><unparsedAffiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="FR" type="organization"><unparsedAffiliation>Univ Lille Nord de France, Lille, France</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="FR" type="organization"><unparsedAffiliation>Movement Disorders Unit, Lille University Hospital, Lille, France</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="FR" type="organization"><unparsedAffiliation>Functional Genomic Platform, UDSL, IRCL, Lille, France</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">Parkinson</keyword><keyword xml:id="kwd2">alpha‐synuclein</keyword><keyword xml:id="kwd3"><i>SNCA</i></keyword><keyword xml:id="kwd4">duplication</keyword><keyword xml:id="kwd5">overexpression</keyword></keywordGroup><fundingInfo><fundingAgency>Univ Lille Nord de France, INSERM, Lille University Hospital, French Ministry of Research</fundingAgency><fundingNumber>PHRC PARKFANORD (2005/1914).</fundingNumber></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Genomic multiplication of the alpha‐synuclein gene (<i>SNCA</i>) locus is one cause of familial Parkinson disease (PD). We performed detailed genomic, <i>SNCA</i> expression level, clinical, neuropsychological and functional imaging analyses of a parkinsonian kindred with a known duplication of the <i>SNCA</i> locus. We demonstrated that the duplication spanned 4.928 Mb (encompassing 31 known and putative genes) and was the largest to have been described at this locus. The presence of several repetitive long interspersed nuclear elements (LINEs) flanking the potential break area suggested that the duplication resulted from a genomic recombination between LINEs. We sequenced the break junction and confirmed the involvement of L1PA2 and L1PA4 in a non‐allelic, homologous recombination. An analysis of mRNA levels in immortalized lymphoblastoid cells and peripheral blood mononuclear cells showed <i>SNCA</i> overexpression in subjects with the duplication, as well as overexpression of 13 other genes highlighting the usefulness of such cell models to study this duplication. Interestingly, abnormal tracer uptake in DaTSCAN<sup>®</sup> imaging correlated with the severity of the clinical symptoms. Our detailed genomic analysis and clinical exploration enabled us to specify the genotype‐phenotype relationship, identify a case of presymptomatic PD and gain insight into the role of LINEs in <i>SNCA</i> locus duplication. © 2011 Wiley‐Liss, Inc.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Communicated by Christine Van Broeckhoven</p></note><note xml:id="fn2"><p>These authors contributed equally to the study</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>SNCA locus duplication carriers: from genetics to Parkinson disease phenotypes</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>SNCA locus duplication carriers: from genetics to Parkinson disease phenotypes</title></titleInfo><name type="personal"><namePart type="given">Eugénie</namePart><namePart type="family">Mutez</namePart><affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</affiliation><affiliation>Univ Lille Nord de France, Lille, France</affiliation><affiliation>Movement Disorders Unit, Lille University Hospital, Lille, France</affiliation><description>These authors contributed equally to the study</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Frédéric</namePart><namePart type="family">Leprêtre</namePart><affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</affiliation><affiliation>Univ Lille Nord de France, Lille, France</affiliation><affiliation>Functional Genomic Platform, UDSL, IRCL, Lille, France</affiliation><description>These authors contributed equally to the study</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Emilie</namePart><namePart type="family">Le Rhun</namePart><affiliation>Movement Disorders Unit, Lille University Hospital, Lille, France</affiliation><description>These authors contributed equally to the study</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lydie</namePart><namePart type="family">Larvor</namePart><affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</affiliation><affiliation>Univ Lille Nord de France, Lille, France</affiliation><description>These authors contributed equally to the study</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Aurélie</namePart><namePart type="family">Duflot</namePart><affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</affiliation><affiliation>Univ Lille Nord de France, Lille, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Vincent</namePart><namePart type="family">Mouroux</namePart><affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</affiliation><affiliation>Univ Lille Nord de France, Lille, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jean‐Pierre</namePart><namePart type="family">Kerckaert</namePart><affiliation>Univ Lille Nord de France, Lille, France</affiliation><affiliation>Functional Genomic Platform, UDSL, IRCL, Lille, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Martin</namePart><namePart type="family">Figeac</namePart><affiliation>Univ Lille Nord de France, Lille, France</affiliation><affiliation>Functional Genomic Platform, UDSL, IRCL, Lille, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kathy</namePart><namePart type="family">Dujardin</namePart><affiliation>Univ Lille Nord de France, Lille, France</affiliation><affiliation>Movement Disorders Unit, Lille University Hospital, Lille, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alain</namePart><namePart type="family">Destée</namePart><affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</affiliation><affiliation>Univ Lille Nord de France, Lille, France</affiliation><affiliation>Movement Disorders Unit, Lille University Hospital, Lille, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Marie‐Christine</namePart><namePart type="family">Chartier‐Harlin</namePart><affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Lille, France</affiliation><affiliation>Univ Lille Nord de France, Lille, France</affiliation><affiliation>UMR 837 INSERM, Team 6, JParc, IRCL, Place de Verdun, 59045 Lille Cedex, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="brief-communication" displayLabel="shortCommunication"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2011-04</dateIssued><dateCaptured encoding="w3cdtf">2010-10-18</dateCaptured><dateValid encoding="w3cdtf">2011-01-12</dateValid><copyrightDate encoding="w3cdtf">2011</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">4</extent><extent unit="tables">1</extent><extent unit="references">29</extent></physicalDescription><abstract lang="en">Genomic multiplication of the alpha‐synuclein gene (SNCA) locus is one cause of familial Parkinson disease (PD). We performed detailed genomic, SNCA expression level, clinical, neuropsychological and functional imaging analyses of a parkinsonian kindred with a known duplication of the SNCA locus. We demonstrated that the duplication spanned 4.928 Mb (encompassing 31 known and putative genes) and was the largest to have been described at this locus. The presence of several repetitive long interspersed nuclear elements (LINEs) flanking the potential break area suggested that the duplication resulted from a genomic recombination between LINEs. We sequenced the break junction and confirmed the involvement of L1PA2 and L1PA4 in a non‐allelic, homologous recombination. An analysis of mRNA levels in immortalized lymphoblastoid cells and peripheral blood mononuclear cells showed SNCA overexpression in subjects with the duplication, as well as overexpression of 13 other genes highlighting the usefulness of such cell models to study this duplication. Interestingly, abnormal tracer uptake in DaTSCAN® imaging correlated with the severity of the clinical symptoms. Our detailed genomic analysis and clinical exploration enabled us to specify the genotype‐phenotype relationship, identify a case of presymptomatic PD and gain insight into the role of LINEs in SNCA locus duplication. © 2011 Wiley‐Liss, Inc.</abstract><note type="content">*Communicated by Christine Van Broeckhoven</note><note type="funding">Univ Lille Nord de France, INSERM, Lille University Hospital, French Ministry of Research - No. PHRC PARKFANORD (2005/1914).; </note><subject lang="en"><genre>keywords</genre><topic>Parkinson</topic><topic>alpha‐synuclein</topic><topic>SNCA</topic><topic>duplication</topic><topic>overexpression</topic></subject><relatedItem type="host"><titleInfo><title>Human Mutation</title></titleInfo><titleInfo type="abbreviated"><title>Hum. Mutat.</title></titleInfo><genre type="journal">journal</genre><subject><genre>article-category</genre><topic>Mutation in Brief</topic></subject><identifier type="ISSN">1059-7794</identifier><identifier type="eISSN">1098-1004</identifier><identifier type="DOI">10.1002/(ISSN)1098-1004</identifier><identifier type="PublisherID">HUMU</identifier><part><date>2011</date><detail type="volume"><caption>vol.</caption><number>32</number></detail><detail type="issue"><caption>no.</caption><number>4</number></detail><extent unit="pages"><start>E2079</start><end>E2090</end><total>12</total></extent></part></relatedItem><identifier type="istex">243F2079A57EA35B36E0946D26003F3E82592C16</identifier><identifier type="DOI">10.1002/humu.21459</identifier><identifier type="ArticleID">HUMU21459</identifier><accessCondition type="use and reproduction" contentType="copyright">© 2011 Wiley‐Liss, Inc.</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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