The number of CAG repeats within the normal allele does not influence the age of onset in Huntington's disease.
Identifieur interne : 001034 ( PubMed/Checkpoint ); précédent : 001033; suivant : 001035The number of CAG repeats within the normal allele does not influence the age of onset in Huntington's disease.
Auteurs : Ji Klempí [République tchèque] ; Jana Zidovská ; Jan Stochl ; V Ra Kebrdlová Ing ; Tereza Uhrová ; Jan RothSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2011.
Descripteurs français
- Wicri :
- geographic : République tchèque.
English descriptors
- KwdEn :
- Adolescent, Adult, Age of Onset, Aged, Czech Republic, Female, Gene Frequency, Genotype, Humans, Huntington Disease (genetics), Logistic Models, Male, Middle Aged, Nerve Tissue Proteins (genetics), Nuclear Proteins (genetics), Proportional Hazards Models, Trinucleotide Repeats (genetics), Young Adult.
- MESH :
- chemical , genetics : Nerve Tissue Proteins, Nuclear Proteins.
- geographic : Czech Republic.
- genetics : Huntington Disease, Trinucleotide Repeats.
- Adolescent, Adult, Age of Onset, Aged, Female, Gene Frequency, Genotype, Humans, Logistic Models, Male, Middle Aged, Proportional Hazards Models, Young Adult.
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.
DOI: 10.1002/mds.23436
PubMed: 21322024
Affiliations:
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last="Zidovská">Jana Zidovská</name></author><author><name sortKey="Stochl, Jan" sort="Stochl, Jan" uniqKey="Stochl J" first="Jan" last="Stochl">Jan Stochl</name></author><author><name sortKey="Ing, V Ra Kebrdlova" sort="Ing, V Ra Kebrdlova" uniqKey="Ing V" first="V Ra Kebrdlová" last="Ing">V Ra Kebrdlová Ing</name></author><author><name sortKey="Uhrova, Tereza" sort="Uhrova, Tereza" uniqKey="Uhrova T" first="Tereza" last="Uhrová">Tereza Uhrová</name></author><author><name sortKey="Roth, Jan" sort="Roth, Jan" uniqKey="Roth J" first="Jan" last="Roth">Jan Roth</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2011">2011</date><idno type="doi">10.1002/mds.23436</idno><idno type="RBID">pubmed:21322024</idno><idno type="pmid">21322024</idno><idno type="wicri:Area/PubMed/Corpus">001434</idno><idno type="wicri:Area/PubMed/Curation">001434</idno><idno 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sort="Zidovska, Jana" uniqKey="Zidovska J" first="Jana" last="Zidovská">Jana Zidovská</name></author><author><name sortKey="Stochl, Jan" sort="Stochl, Jan" uniqKey="Stochl J" first="Jan" last="Stochl">Jan Stochl</name></author><author><name sortKey="Ing, V Ra Kebrdlova" sort="Ing, V Ra Kebrdlova" uniqKey="Ing V" first="V Ra Kebrdlová" last="Ing">V Ra Kebrdlová Ing</name></author><author><name sortKey="Uhrova, Tereza" sort="Uhrova, Tereza" uniqKey="Uhrova T" first="Tereza" last="Uhrová">Tereza Uhrová</name></author><author><name sortKey="Roth, Jan" sort="Roth, Jan" uniqKey="Roth J" first="Jan" last="Roth">Jan Roth</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2011" type="published">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Age of Onset</term><term>Aged</term><term>Czech Republic</term><term>Female</term><term>Gene Frequency</term><term>Genotype</term><term>Humans</term><term>Huntington Disease (genetics)</term><term>Logistic Models</term><term>Male</term><term>Middle Aged</term><term>Nerve Tissue Proteins (genetics)</term><term>Nuclear Proteins (genetics)</term><term>Proportional Hazards Models</term><term>Trinucleotide Repeats (genetics)</term><term>Young Adult</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Nerve Tissue Proteins</term><term>Nuclear Proteins</term></keywords><keywords scheme="MESH" type="geographic" xml:lang="en"><term>Czech Republic</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Huntington Disease</term><term>Trinucleotide Repeats</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Age of Onset</term><term>Aged</term><term>Female</term><term>Gene Frequency</term><term>Genotype</term><term>Humans</term><term>Logistic Models</term><term>Male</term><term>Middle Aged</term><term>Proportional Hazards Models</term><term>Young Adult</term></keywords><keywords scheme="Wicri" type="geographic" xml:lang="fr"><term>République tchèque</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml: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.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">21322024</PMID><DateCreated><Year>2011</Year><Month>02</Month><Day>15</Day></DateCreated><DateCompleted><Year>2011</Year><Month>06</Month><Day>06</Day></DateCompleted><DateRevised><Year>2012</Year><Month>07</Month><Day>11</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1531-8257</ISSN><JournalIssue CitedMedium="Internet"><Volume>26</Volume><Issue>1</Issue><PubDate><Year>2011</Year><Month>Jan</Month></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>The number of CAG repeats within the normal allele does not influence the age of onset in Huntington's disease.</ArticleTitle><Pagination><MedlinePgn>125-9</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/mds.23436</ELocationID><Abstract><AbstractText>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.</AbstractText><CopyrightInformation>Copyright © 2010 Movement Disorder Society.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Klempíř</LastName><ForeName>Jiří</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Neurology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic. jiri.klempir@seznam.cz</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zidovská</LastName><ForeName>Jana</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Stochl</LastName><ForeName>Jan</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Ing</LastName><ForeName>Věra Kebrdlová</ForeName><Initials>VK</Initials></Author><Author ValidYN="Y"><LastName>Uhrová</LastName><ForeName>Tereza</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Roth</LastName><ForeName>Jan</ForeName><Initials>J</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2010</Year><Month>11</Month><Day>10</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mov Disord</MedlineTA><NlmUniqueID>8610688</NlmUniqueID><ISSNLinking>0885-3185</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C086055">HTT protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009419">Nerve Tissue Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009687">Nuclear Proteins</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>Mov Disord. 2011 Nov;26(13):2450-1; author reply 2451</RefSource><PMID Version="1">22109852</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000293">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000328">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D017668">Age of Onset</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000368">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" Type="Geographic" UI="D018153">Czech Republic</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D005260">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D005787">Gene Frequency</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D005838">Genotype</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006801">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006816">Huntington Disease</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D016015">Logistic Models</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008297">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008875">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D009419">Nerve Tissue Proteins</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D009687">Nuclear Proteins</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D016016">Proportional Hazards Models</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D018911">Trinucleotide Repeats</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D055815">Young Adult</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2010</Year><Month>3</Month><Day>23</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2010</Year><Month>6</Month><Day>24</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2010</Year><Month>8</Month><Day>11</Day></PubMedPubDate><PubMedPubDate PubStatus="aheadofprint"><Year>2010</Year><Month>11</Month><Day>10</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2011</Year><Month>2</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2011</Year><Month>2</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2011</Year><Month>6</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="doi">10.1002/mds.23436</ArticleId><ArticleId IdType="pubmed">21322024</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>République tchèque</li></country><region><li>Bohême centrale</li></region><settlement><li>Prague</li></settlement></list><tree><noCountry><name sortKey="Ing, V Ra Kebrdlova" sort="Ing, V Ra Kebrdlova" uniqKey="Ing V" first="V Ra Kebrdlová" last="Ing">V Ra Kebrdlová Ing</name><name sortKey="Roth, Jan" sort="Roth, Jan" uniqKey="Roth J" first="Jan" last="Roth">Jan Roth</name><name sortKey="Stochl, Jan" sort="Stochl, Jan" uniqKey="Stochl J" first="Jan" last="Stochl">Jan Stochl</name><name sortKey="Uhrova, Tereza" sort="Uhrova, Tereza" uniqKey="Uhrova T" first="Tereza" last="Uhrová">Tereza Uhrová</name><name sortKey="Zidovska, Jana" sort="Zidovska, Jana" uniqKey="Zidovska J" first="Jana" last="Zidovská">Jana Zidovská</name></noCountry><country name="République tchèque"><region name="Bohême centrale"><name sortKey="Klempi, Ji" sort="Klempi, Ji" uniqKey="Klempi J" first="Ji" last="Klempí">Ji Klempí</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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