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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16</title><author><name sortKey="Djousse, Luc" sort="Djousse, Luc" uniqKey="Djousse L" first="Luc" last="Djoussé">Luc Djoussé</name></author><author><name sortKey="Knowlton, Beth" sort="Knowlton, Beth" uniqKey="Knowlton B" first="Beth" last="Knowlton">Beth Knowlton</name></author><author><name sortKey="Hayden, Michael R" sort="Hayden, Michael R" uniqKey="Hayden M" first="Michael R." last="Hayden">Michael R. Hayden</name></author><author><name sortKey="Almqvist, Elisabeth W" sort="Almqvist, Elisabeth W" uniqKey="Almqvist E" first="Elisabeth W." last="Almqvist">Elisabeth W. Almqvist</name></author><author><name sortKey="Brinkman, Ryan R" sort="Brinkman, Ryan R" uniqKey="Brinkman R" first="Ryan R." last="Brinkman">Ryan R. Brinkman</name></author><author><name sortKey="Ross, Christopher A" sort="Ross, Christopher A" uniqKey="Ross C" first="Christopher A." last="Ross">Christopher A. Ross</name></author><author><name sortKey="Margolis, Russel L" sort="Margolis, Russel L" uniqKey="Margolis R" first="Russel L." last="Margolis">Russel L. Margolis</name></author><author><name sortKey="Rosenblatt, Adam" sort="Rosenblatt, Adam" uniqKey="Rosenblatt A" first="Adam" last="Rosenblatt">Adam Rosenblatt</name></author><author><name sortKey="Durr, Alexandra" sort="Durr, Alexandra" uniqKey="Durr A" first="Alexandra" last="Durr">Alexandra Durr</name></author><author><name sortKey="Dode, Catherine" sort="Dode, Catherine" uniqKey="Dode C" first="Catherine" last="Dode">Catherine Dode</name></author><author><name sortKey="Morrison, Patrick J" sort="Morrison, Patrick J" uniqKey="Morrison P" first="Patrick J." last="Morrison">Patrick J. Morrison</name></author><author><name sortKey="Novelletto, Andrea" sort="Novelletto, Andrea" uniqKey="Novelletto A" first="Andrea" last="Novelletto">Andrea Novelletto</name></author><author><name sortKey="Frontali, Marina" sort="Frontali, Marina" uniqKey="Frontali M" first="Marina" last="Frontali">Marina Frontali</name></author><author><name sortKey="Trent, Ronald J A" sort="Trent, Ronald J A" uniqKey="Trent R" first="Ronald J. A." last="Trent">Ronald J. A. Trent</name></author><author><name sortKey="Mccusker, Elizabeth" sort="Mccusker, Elizabeth" uniqKey="Mccusker E" first="Elizabeth" last="Mccusker">Elizabeth Mccusker</name></author><author><name sortKey="G Mez Tortosa, Estrella" sort="G Mez Tortosa, Estrella" uniqKey="G Mez Tortosa E" first="Estrella" last="G Mez-Tortosa">Estrella G Mez-Tortosa</name></author><author><name sortKey="Mayo Cabrero, David" sort="Mayo Cabrero, David" uniqKey="Mayo Cabrero D" first="David" last="Mayo Cabrero">David Mayo Cabrero</name></author><author><name sortKey="Jones, Randi" sort="Jones, Randi" uniqKey="Jones R" first="Randi" last="Jones">Randi Jones</name></author><author><name sortKey="Zanko, Andrea" sort="Zanko, Andrea" uniqKey="Zanko A" first="Andrea" last="Zanko">Andrea Zanko</name></author><author><name sortKey="Nance, Martha" sort="Nance, Martha" uniqKey="Nance M" first="Martha" last="Nance">Martha Nance</name></author><author><name sortKey="Abramson, Ruth K" sort="Abramson, Ruth K" uniqKey="Abramson R" first="Ruth K." last="Abramson">Ruth K. Abramson</name></author><author><name sortKey="Suchowersky, Oksana" sort="Suchowersky, Oksana" uniqKey="Suchowersky O" first="Oksana" last="Suchowersky">Oksana Suchowersky</name></author><author><name sortKey="Paulsen, Jane S" sort="Paulsen, Jane S" uniqKey="Paulsen J" first="Jane S." last="Paulsen">Jane S. Paulsen</name></author><author><name sortKey="Harrison, Madaline B" sort="Harrison, Madaline B" uniqKey="Harrison M" first="Madaline B." last="Harrison">Madaline B. Harrison</name></author><author><name sortKey="Yang, Qiong" sort="Yang, Qiong" uniqKey="Yang Q" first="Qiong" last="Yang">Qiong Yang</name></author><author><name sortKey="Cupples, L Adrienne" sort="Cupples, L Adrienne" uniqKey="Cupples L" first="L. Adrienne" last="Cupples">L. Adrienne Cupples</name></author><author><name sortKey="Mysore, Jayalakshmi" sort="Mysore, Jayalakshmi" uniqKey="Mysore J" first="Jayalakshmi" last="Mysore">Jayalakshmi Mysore</name></author><author><name sortKey="Gusella, James F" sort="Gusella, James F" uniqKey="Gusella J" first="James F." last="Gusella">James F. Gusella</name></author><author><name sortKey="Macdonald, Marcy E" sort="Macdonald, Marcy E" uniqKey="Macdonald M" first="Marcy E." last="Macdonald">Marcy E. Macdonald</name></author><author><name sortKey="Myers, Richard H" sort="Myers, Richard H" uniqKey="Myers R" first="Richard H." last="Myers">Richard H. Myers</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">15029481</idno><idno type="pmc">1866166</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1866166</idno><idno type="RBID">PMC:1866166</idno><idno type="doi">10.1007/s10048-004-0175-2</idno><date when="2004">2004</date><idno type="wicri:Area/Pmc/Corpus">002208</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002208</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16</title><author><name sortKey="Djousse, Luc" sort="Djousse, Luc" uniqKey="Djousse L" first="Luc" last="Djoussé">Luc Djoussé</name></author><author><name sortKey="Knowlton, Beth" sort="Knowlton, Beth" uniqKey="Knowlton B" first="Beth" last="Knowlton">Beth Knowlton</name></author><author><name sortKey="Hayden, Michael R" sort="Hayden, Michael R" uniqKey="Hayden M" first="Michael R." last="Hayden">Michael R. Hayden</name></author><author><name sortKey="Almqvist, Elisabeth W" sort="Almqvist, Elisabeth W" uniqKey="Almqvist E" first="Elisabeth W." last="Almqvist">Elisabeth W. Almqvist</name></author><author><name sortKey="Brinkman, Ryan R" sort="Brinkman, Ryan R" uniqKey="Brinkman R" first="Ryan R." last="Brinkman">Ryan R. Brinkman</name></author><author><name sortKey="Ross, Christopher A" sort="Ross, Christopher A" uniqKey="Ross C" first="Christopher A." last="Ross">Christopher A. Ross</name></author><author><name sortKey="Margolis, Russel L" sort="Margolis, Russel L" uniqKey="Margolis R" first="Russel L." last="Margolis">Russel L. Margolis</name></author><author><name sortKey="Rosenblatt, Adam" sort="Rosenblatt, Adam" uniqKey="Rosenblatt A" first="Adam" last="Rosenblatt">Adam Rosenblatt</name></author><author><name sortKey="Durr, Alexandra" sort="Durr, Alexandra" uniqKey="Durr A" first="Alexandra" last="Durr">Alexandra Durr</name></author><author><name sortKey="Dode, Catherine" sort="Dode, Catherine" uniqKey="Dode C" first="Catherine" last="Dode">Catherine Dode</name></author><author><name sortKey="Morrison, Patrick J" sort="Morrison, Patrick J" uniqKey="Morrison P" first="Patrick J." last="Morrison">Patrick J. Morrison</name></author><author><name sortKey="Novelletto, Andrea" sort="Novelletto, Andrea" uniqKey="Novelletto A" first="Andrea" last="Novelletto">Andrea Novelletto</name></author><author><name sortKey="Frontali, Marina" sort="Frontali, Marina" uniqKey="Frontali M" first="Marina" last="Frontali">Marina Frontali</name></author><author><name sortKey="Trent, Ronald J A" sort="Trent, Ronald J A" uniqKey="Trent R" first="Ronald J. A." last="Trent">Ronald J. A. Trent</name></author><author><name sortKey="Mccusker, Elizabeth" sort="Mccusker, Elizabeth" uniqKey="Mccusker E" first="Elizabeth" last="Mccusker">Elizabeth Mccusker</name></author><author><name sortKey="G Mez Tortosa, Estrella" sort="G Mez Tortosa, Estrella" uniqKey="G Mez Tortosa E" first="Estrella" last="G Mez-Tortosa">Estrella G Mez-Tortosa</name></author><author><name sortKey="Mayo Cabrero, David" sort="Mayo Cabrero, David" uniqKey="Mayo Cabrero D" first="David" last="Mayo Cabrero">David Mayo Cabrero</name></author><author><name sortKey="Jones, Randi" sort="Jones, Randi" uniqKey="Jones R" first="Randi" last="Jones">Randi Jones</name></author><author><name sortKey="Zanko, Andrea" sort="Zanko, Andrea" uniqKey="Zanko A" first="Andrea" last="Zanko">Andrea Zanko</name></author><author><name sortKey="Nance, Martha" sort="Nance, Martha" uniqKey="Nance M" first="Martha" last="Nance">Martha Nance</name></author><author><name sortKey="Abramson, Ruth K" sort="Abramson, Ruth K" uniqKey="Abramson R" first="Ruth K." last="Abramson">Ruth K. Abramson</name></author><author><name sortKey="Suchowersky, Oksana" sort="Suchowersky, Oksana" uniqKey="Suchowersky O" first="Oksana" last="Suchowersky">Oksana Suchowersky</name></author><author><name sortKey="Paulsen, Jane S" sort="Paulsen, Jane S" uniqKey="Paulsen J" first="Jane S." last="Paulsen">Jane S. Paulsen</name></author><author><name sortKey="Harrison, Madaline B" sort="Harrison, Madaline B" uniqKey="Harrison M" first="Madaline B." last="Harrison">Madaline B. Harrison</name></author><author><name sortKey="Yang, Qiong" sort="Yang, Qiong" uniqKey="Yang Q" first="Qiong" last="Yang">Qiong Yang</name></author><author><name sortKey="Cupples, L Adrienne" sort="Cupples, L Adrienne" uniqKey="Cupples L" first="L. Adrienne" last="Cupples">L. Adrienne Cupples</name></author><author><name sortKey="Mysore, Jayalakshmi" sort="Mysore, Jayalakshmi" uniqKey="Mysore J" first="Jayalakshmi" last="Mysore">Jayalakshmi Mysore</name></author><author><name sortKey="Gusella, James F" sort="Gusella, James F" uniqKey="Gusella J" first="James F." last="Gusella">James F. Gusella</name></author><author><name sortKey="Macdonald, Marcy E" sort="Macdonald, Marcy E" uniqKey="Macdonald M" first="Marcy E." last="Macdonald">Marcy E. Macdonald</name></author><author><name sortKey="Myers, Richard H" sort="Myers, Richard H" uniqKey="Myers R" first="Richard H." last="Myers">Richard H. Myers</name></author></analytic><series><title level="j">Neurogenetics</title><idno type="ISSN">1364-6745</idno><idno type="eISSN">1364-6753</idno><imprint><date when="2004">2004</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the <italic>HD</italic> gene on chromosome 4p16.3. A recent genome scan for genetic modifiers of age at onset of motor symptoms (AO) in HD suggests that one modifier may reside in the region close to the <italic>HD</italic> gene itself. We used data from 535 HD participants of the New England Huntington cohort and the HD MAPS cohort to assess whether AO was influenced by any of the three markers in the 4p16 region: <italic>MSX1</italic> (<italic>Drosophila</italic> homeo box homologue 1, formerly known as homeo box 7, <italic>HOX7</italic>), Δ<italic>2642</italic> (within the <italic>HD</italic> coding sequence), and <italic>BJ56</italic> (<italic>D4S127</italic>). Suggestive evidence for an association was seen between <italic>MSX1</italic> alleles and AO, after adjustment for normal CAG repeat, expanded repeat, and their product term (model <italic>P</italic> value 0.079). Of the variance of AO that was not accounted for by HD and normal CAG repeats, 0.8% could be attributed to the <italic>MSX1</italic> genotype. Individuals with <italic>MSX1</italic> genotype 3/3 tended to have younger AO. No association was found between Δ2642 (<italic>P</italic>=0.44) and <italic>BJ56</italic> (<italic>P</italic>=0.73) and AO. This study supports previous studies suggesting that there may be a significant genetic modifier for AO in HD in the 4p16 region. Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the <italic>MSX1</italic> marker.</p></div></front></TEI><pmc article-type="research-article"><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">9709714</journal-id><journal-id journal-id-type="pubmed-jr-id">20757</journal-id><journal-id journal-id-type="nlm-ta">Neurogenetics</journal-id><journal-title>Neurogenetics</journal-title><issn pub-type="ppub">1364-6745</issn><issn pub-type="epub">1364-6753</issn></journal-meta><article-meta><article-id pub-id-type="pmid">15029481</article-id><article-id pub-id-type="pmc">1866166</article-id><article-id pub-id-type="doi">10.1007/s10048-004-0175-2</article-id><article-id pub-id-type="manuscript">NIHMS2838</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Djoussé</surname><given-names>Luc</given-names></name><aff id="A1">Evans Department of Medicine, Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts, USA</aff></contrib><contrib contrib-type="author"><name><surname>Knowlton</surname><given-names>Beth</given-names></name><aff id="A2">Department of Neurology, Boston University School of Medicine, 715 Albany Street, Boston, Massachusetts, MA 02118, USA</aff></contrib><contrib contrib-type="author"><name><surname>Hayden</surname><given-names>Michael R.</given-names></name><aff id="A3">Center for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada</aff></contrib><contrib contrib-type="author"><name><surname>Almqvist</surname><given-names>Elisabeth W.</given-names></name><aff id="A4">Center for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada</aff></contrib><contrib contrib-type="author"><name><surname>Brinkman</surname><given-names>Ryan R.</given-names></name><aff id="A5">Center for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada</aff></contrib><contrib contrib-type="author"><name><surname>Ross</surname><given-names>Christopher A.</given-names></name><aff id="A6">Department of Psychiatry, Johns Hopkins University, Baltimore, Maryland, USA</aff></contrib><contrib contrib-type="author"><name><surname>Margolis</surname><given-names>Russel L.</given-names></name><aff id="A7">Department of Psychiatry, Johns Hopkins University, Baltimore, Maryland, USA</aff></contrib><contrib contrib-type="author"><name><surname>Rosenblatt</surname><given-names>Adam</given-names></name><aff id="A8">Department of Psychiatry, Johns Hopkins University, Baltimore, Maryland, USA</aff></contrib><contrib contrib-type="author"><name><surname>Durr</surname><given-names>Alexandra</given-names></name><aff id="A9">Hopital de la Salpetriere, Paris, France</aff></contrib><contrib contrib-type="author"><name><surname>Dode</surname><given-names>Catherine</given-names></name><aff id="A10">Hopital de la Salpetriere, Paris, France</aff></contrib><contrib contrib-type="author"><name><surname>Morrison</surname><given-names>Patrick J.</given-names></name><aff id="A11">Department of Medical Genetics, Belfast City Hospital Trust, Belfast, UK</aff></contrib><contrib contrib-type="author"><name><surname>Novelletto</surname><given-names>Andrea</given-names></name><aff id="A12">Department of Cell Biology, University of Calabria, Rende, Italy</aff></contrib><contrib contrib-type="author"><name><surname>Frontali</surname><given-names>Marina</given-names></name><aff id="A13">Institute of Experimental Medicine, CNR, Rome, Italy</aff></contrib><contrib contrib-type="author"><name><surname>Trent</surname><given-names>Ronald J. A.</given-names></name><aff id="A14">Department of Medicine, University of Sydney, Sydney, Australia</aff></contrib><contrib contrib-type="author"><name><surname>McCusker</surname><given-names>Elizabeth</given-names></name><aff id="A15">Neurology Department, Westmead Hospital, Sydney, Australia</aff></contrib><contrib contrib-type="author"><name><surname>Gómez-Tortosa</surname><given-names>Estrella</given-names></name><aff id="A16">Servicio de Neurología y Genética, Fundación Jiménez Díaz, Madrid, Spain</aff></contrib><contrib contrib-type="author"><name><surname>Mayo Cabrero</surname><given-names>David</given-names></name><aff id="A17">Servicio de Neurología y Genética, Fundación Jiménez Díaz, Madrid, Spain</aff></contrib><contrib contrib-type="author"><name><surname>Jones</surname><given-names>Randi</given-names></name><aff id="A18">Emory Neurobehavioral Center, Atlanta, Georgia, USA</aff></contrib><contrib contrib-type="author"><name><surname>Zanko</surname><given-names>Andrea</given-names></name><aff id="A19">UCSF Division of Medical Genetics, San Francisco, California, USA</aff></contrib><contrib contrib-type="author"><name><surname>Nance</surname><given-names>Martha</given-names></name><aff id="A20">Department of Neurology, Hennepin County Medical Center, Minneapolis, Minnesota, USA</aff></contrib><contrib contrib-type="author"><name><surname>Abramson</surname><given-names>Ruth K.</given-names></name><aff id="A21">Department of Neuropsychiatry and Behavior, WMS Hall Psychiatric Institute, Columbia, South Carolina, USA</aff></contrib><contrib contrib-type="author"><name><surname>Suchowersky</surname><given-names>Oksana</given-names></name><aff id="A22">Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada</aff></contrib><contrib contrib-type="author"><name><surname>Paulsen</surname><given-names>Jane S.</given-names></name><aff id="A23">Department of Psychiatry, University of Iowa, Iowa City, Iowa, USA</aff></contrib><contrib contrib-type="author"><name><surname>Harrison</surname><given-names>Madaline B.</given-names></name><aff id="A24">Department of Neurology, University of Virginia, Charlottesville, Virginia, USA</aff></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Qiong</given-names></name><aff id="A25">Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA</aff></contrib><contrib contrib-type="author"><name><surname>Cupples</surname><given-names>L. Adrienne</given-names></name><aff id="A26">Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA</aff></contrib><contrib contrib-type="author"><name><surname>Mysore</surname><given-names>Jayalakshmi</given-names></name><aff id="A27">Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA</aff></contrib><contrib contrib-type="author"><name><surname>Gusella</surname><given-names>James F.</given-names></name><aff id="A28">Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA</aff></contrib><contrib contrib-type="author"><name><surname>MacDonald</surname><given-names>Marcy E.</given-names></name><aff id="A29">Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA</aff></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Myers</surname><given-names>Richard H.</given-names></name><aff id="A30">Evans Department of Medicine, Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts, USA, Department of Neurology, Boston University School of Medicine, 715 Albany Street, Boston, Massachusetts, MA 02118, USA, e-mail:<email>rmyers@bu.edu</email>, Tel.: +1-617-6385376, Fax: +1-617-6388076</aff></contrib></contrib-group><pub-date pub-type="nihms-submitted"><day>27</day><month>3</month><year>2007</year></pub-date><pub-date pub-type="epub"><day>17</day><month>3</month><year>2004</year></pub-date><pub-date pub-type="ppub"><month>6</month><year>2004</year></pub-date><pub-date pub-type="pmc-release"><day>7</day><month>5</month><year>2007</year></pub-date><volume>5</volume><issue>2</issue><fpage>109</fpage><lpage>114</lpage><abstract><p id="P1">Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the <italic>HD</italic> gene on chromosome 4p16.3. A recent genome scan for genetic modifiers of age at onset of motor symptoms (AO) in HD suggests that one modifier may reside in the region close to the <italic>HD</italic> gene itself. We used data from 535 HD participants of the New England Huntington cohort and the HD MAPS cohort to assess whether AO was influenced by any of the three markers in the 4p16 region: <italic>MSX1</italic> (<italic>Drosophila</italic> homeo box homologue 1, formerly known as homeo box 7, <italic>HOX7</italic>), Δ<italic>2642</italic> (within the <italic>HD</italic> coding sequence), and <italic>BJ56</italic> (<italic>D4S127</italic>). Suggestive evidence for an association was seen between <italic>MSX1</italic> alleles and AO, after adjustment for normal CAG repeat, expanded repeat, and their product term (model <italic>P</italic> value 0.079). Of the variance of AO that was not accounted for by HD and normal CAG repeats, 0.8% could be attributed to the <italic>MSX1</italic> genotype. Individuals with <italic>MSX1</italic> genotype 3/3 tended to have younger AO. No association was found between Δ2642 (<italic>P</italic>=0.44) and <italic>BJ56</italic> (<italic>P</italic>=0.73) and AO. This study supports previous studies suggesting that there may be a significant genetic modifier for AO in HD in the 4p16 region. Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the <italic>MSX1</italic> marker.</p></abstract><kwd-group><kwd>Huntington disease</kwd><kwd>Modifier</kwd><kwd>Onset age</kwd><kwd>Genetics</kwd><kwd>Trinucleotide repeat</kwd><kwd>HD gene</kwd></kwd-group><contract-num rid="NS1">P50 NS016367-26A18782</contract-num><contract-sponsor id="NS1">National Institute of Neurological Disorders and Stroke : NINDS</contract-sponsor></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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