The number of CAG repeats within the normal allele does not influence the age of onset in Huntington's disease
Identifieur interne : 001234 ( Istex/Corpus ); précédent : 001233; suivant : 001235The number of CAG repeats within the normal allele does not influence the age of onset in Huntington's disease
Auteurs : Ji Klempí ; Jana Židovská ; Jan Štochl ; V Ra Kebrdlová Ing ; Tereza Uhrová ; Jan RothSource :
- Movement Disorders [ 0885-3185 ] ; 2011-01.
English descriptors
- KwdEn :
Abstract
Huntington's disease (HD) is caused by the expansion of the number of CAG repeats on the chromosome 4p16.3, which results in elongated glutamine tract of huntingtin. The purpose of this work was to examine the interaction between the normal and mutant alleles of this gene and their effect on the clinical onset of HD. We hypothesized that in patients with identical number of CAG repeats within the mutant allele, the age of onset of HD is influenced by the number of CAG repeats within the normal allele. We analyzed the relations between the number of CAG repeats within the normal and mutant alleles, the age at HD onset, and the character of initial symptoms in 468 patients with clinically expressed HD. Although the Cox regression coefficient of 0.15 was significant (P < 0.0001), the regression model explained only 28% of the variance of the age at onset related to the effect of the number of CAG repeats within normal allele. Within the groups of patients with the same number of CAG repeats of the mutant allele, number of CAG repeats of the normal allele was found uncorrelated to the age at onset. Furthermore, when analyzing subgroups of patients with the same allelic composition on both alleles, we failed to observe any correlation with the age at the onset. Our analysis gives no corroboration to the idea of a normal allele having a share in the modification of the age at HD onset. We believe that with the current state of knowledge it is not possible to devise a mathematical model for HD onset prediction because too many entirely unknown modifying factors are still involved. © 2010 Movement Disorder Society
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DOI: 10.1002/mds.23436
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ISTEX:0DE1F3F64D5CF0DE8A548E37E24640FA5AAF6B4DLe document en format XML
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The purpose of this work was to examine the interaction between the normal and mutant alleles of this gene and their effect on the clinical onset of HD. We hypothesized that in patients with identical number of CAG repeats within the mutant allele, the age of onset of HD is influenced by the number of CAG repeats within the normal allele. We analyzed the relations between the number of CAG repeats within the normal and mutant alleles, the age at HD onset, and the character of initial symptoms in 468 patients with clinically expressed HD. Although the Cox regression coefficient of 0.15 was significant (P < 0.0001), the regression model explained only 28% of the variance of the age at onset related to the effect of the number of CAG repeats within normal allele. Within the groups of patients with the same number of CAG repeats of the mutant allele, number of CAG repeats of the normal allele was found uncorrelated to the age at onset. Furthermore, when analyzing subgroups of patients with the same allelic composition on both alleles, we failed to observe any correlation with the age at the onset. Our analysis gives no corroboration to the idea of a normal allele having a share in the modification of the age at HD onset. We believe that with the current state of knowledge it is not possible to devise a mathematical model for HD onset prediction because too many entirely unknown modifying factors are still involved. © 2010 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Jiří Klempíř MD, PhD</name><affiliations><json:string>Department of Neurology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic</json:string></affiliations></json:item><json:item><name>Jana Židovská MD, PhD</name><affiliations><json:string>Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic</json:string></affiliations></json:item><json:item><name>Jan Štochl PhD</name><affiliations><json:string>Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom</json:string></affiliations></json:item><json:item><name>Věra Kebrdlová Ing</name><affiliations><json:string>Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic</json:string></affiliations></json:item><json:item><name>Tereza Uhrová MD</name><affiliations><json:string>Department of Psychiatry, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic</json:string></affiliations></json:item><json:item><name>Jan Roth MD, PhD</name><affiliations><json:string>Department of Neurology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Huntington's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>CAG triplet</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>age at onset</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Huntington's disease (HD) is caused by the expansion of the number of CAG repeats on the chromosome 4p16.3, which results in elongated glutamine tract of huntingtin. 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Furthermore, when analyzing subgroups of patients with the same allelic composition on both alleles, we failed to observe any correlation with the age at the onset. Our analysis gives no corroboration to the idea of a normal allele having a share in the modification of the age at HD onset. 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The purpose of this work was to examine the interaction between the normal and mutant alleles of this gene and their effect on the clinical onset of HD. We hypothesized that in patients with identical number of CAG repeats within the mutant allele, the age of onset of HD is influenced by the number of CAG repeats within the normal allele. We analyzed the relations between the number of CAG repeats within the normal and mutant alleles, the age at HD onset, and the character of initial symptoms in 468 patients with clinically expressed HD. Although the Cox regression coefficient of 0.15 was significant (P < 0.0001), the regression model explained only 28% of the variance of the age at onset related to the effect of the number of CAG repeats within normal allele. Within the groups of patients with the same number of CAG repeats of the mutant allele, number of CAG repeats of the normal allele was found uncorrelated to the age at onset. Furthermore, when analyzing subgroups of patients with the same allelic composition on both alleles, we failed to observe any correlation with the age at the onset. Our analysis gives no corroboration to the idea of a normal allele having a share in the modification of the age at HD onset. We believe that with the current state of knowledge it is not possible to devise a mathematical model for HD onset prediction because too many entirely unknown modifying factors are still involved. © 2010 Movement Disorder Society</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Huntington's disease</term></item><item><term>CAG triplet</term></item><item><term>age at onset</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>Article category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2010-03-23">Received</change><change when="2010-08-11">Registration</change><change when="2011-01">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/0DE1F3F64D5CF0DE8A548E37E24640FA5AAF6B4D/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><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)1531-8257</doi><issn type="print">0885-3185</issn><issn type="electronic">1531-8257</issn><idGroup><id type="product" value="MDS"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="MOVEMENT DISORDERS">Movement Disorders</title><title type="short">Mov. 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disease</keyword><keyword xml:id="kwd2">CAG triplet</keyword><keyword xml:id="kwd3">age at onset</keyword></keywordGroup><fundingInfo><fundingAgency>Czech Ministry of Education Research Programs</fundingAgency><fundingNumber>MSM0021620849</fundingNumber></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Huntington's disease (HD) is caused by the expansion of the number of CAG repeats on the chromosome 4p16.3, which results in elongated glutamine tract of huntingtin. The purpose of this work was to examine the interaction between the normal and mutant alleles of this gene and their effect on the clinical onset of HD. We hypothesized that in patients with identical number of CAG repeats within the mutant allele, the age of onset of HD is influenced by the number of CAG repeats within the normal allele. We analyzed the relations between the number of CAG repeats within the normal and mutant alleles, the age at HD onset, and the character of initial symptoms in 468 patients with clinically expressed HD. Although the Cox regression coefficient of 0.15 was significant (<i>P</i> < 0.0001), the regression model explained only 28% of the variance of the age at onset related to the effect of the number of CAG repeats within normal allele. Within the groups of patients with the same number of CAG repeats of the mutant allele, number of CAG repeats of the normal allele was found uncorrelated to the age at onset. Furthermore, when analyzing subgroups of patients with the same allelic composition on both alleles, we failed to observe any correlation with the age at the onset. Our analysis gives no corroboration to the idea of a normal allele having a share in the modification of the age at HD onset. We believe that with the current state of knowledge it is not possible to devise a mathematical model for HD onset prediction because too many entirely unknown modifying factors are still involved. © 2010 Movement Disorder Society</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Potential conflict of interest: There are no conflicts of interest.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><!--Version 0.6 générée le 4-12-2015--><mods version="3.6"><titleInfo lang="en"><title>The number of CAG repeats within the normal allele does not influence the age of onset in Huntington's disease</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Normal Allele Does Not Influence the Age of Onset in HD</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>The number of CAG repeats within the normal allele does not influence the age of onset in Huntington's disease</title></titleInfo><name type="personal"><namePart type="given">Jiří</namePart><namePart type="family">Klempíř</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic</affiliation><description>Correspondence: Department of Neurology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Kateřinská 30, 12000 Prague 2, Czech Republic</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jana</namePart><namePart type="family">Židovská</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jan</namePart><namePart type="family">Štochl</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Věra Kebrdlová</namePart><namePart type="family">Ing</namePart><affiliation>Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Tereza</namePart><namePart type="family">Uhrová</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Psychiatry, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jan</namePart><namePart type="family">Roth</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre authority="originalCategForm">article</genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2011-01</dateIssued><dateCaptured encoding="w3cdtf">2010-03-23</dateCaptured><dateValid encoding="w3cdtf">2010-08-11</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">1</extent><extent unit="tables">2</extent><extent unit="references">40</extent><extent unit="words">4621</extent></physicalDescription><abstract lang="en">Huntington's disease (HD) is caused by the expansion of the number of CAG repeats on the chromosome 4p16.3, which results in elongated glutamine tract of huntingtin. The purpose of this work was to examine the interaction between the normal and mutant alleles of this gene and their effect on the clinical onset of HD. We hypothesized that in patients with identical number of CAG repeats within the mutant allele, the age of onset of HD is influenced by the number of CAG repeats within the normal allele. We analyzed the relations between the number of CAG repeats within the normal and mutant alleles, the age at HD onset, and the character of initial symptoms in 468 patients with clinically expressed HD. Although the Cox regression coefficient of 0.15 was significant (P < 0.0001), the regression model explained only 28% of the variance of the age at onset related to the effect of the number of CAG repeats within normal allele. Within the groups of patients with the same number of CAG repeats of the mutant allele, number of CAG repeats of the normal allele was found uncorrelated to the age at onset. Furthermore, when analyzing subgroups of patients with the same allelic composition on both alleles, we failed to observe any correlation with the age at the onset. Our analysis gives no corroboration to the idea of a normal allele having a share in the modification of the age at HD onset. We believe that with the current state of knowledge it is not possible to devise a mathematical model for HD onset prediction because too many entirely unknown modifying factors are still involved. © 2010 Movement Disorder Society</abstract><note type="content">*Potential conflict of interest: There are no conflicts of interest.</note><note type="funding">Czech Ministry of Education Research Programs - No. MSM0021620849; </note><subject lang="en"><genre>Keywords</genre><topic>Huntington's disease</topic><topic>CAG triplet</topic><topic>age at onset</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title></titleInfo><titleInfo type="abbreviated"><title>Mov. Disord.</title></titleInfo><subject><genre>article category</genre><topic>Research Article</topic></subject><identifier type="ISSN">0885-3185</identifier><identifier type="eISSN">1531-8257</identifier><identifier type="DOI">10.1002/(ISSN)1531-8257</identifier><identifier type="PublisherID">MDS</identifier><part><date>2011</date><detail type="volume"><caption>vol.</caption><number>26</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>125</start><end>129</end><total>5</total></extent></part></relatedItem><identifier type="istex">0DE1F3F64D5CF0DE8A548E37E24640FA5AAF6B4D</identifier><identifier type="DOI">10.1002/mds.23436</identifier><identifier type="ArticleID">MDS23436</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2010 Movement Disorder Society</accessCondition><recordInfo><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin><recordContentSource>WILEY</recordContentSource></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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