The number of CAG repeats within the normal allele does not influence the age of onset in Huntington's disease
Identifieur interne : 001320 ( Main/Exploration ); précédent : 001319; suivant : 001321The 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 Židovská [République tchèque] ; Jan Štochl [Royaume-Uni] ; V Ra Kebrdlová Ing [République tchèque] ; Tereza Uhrová [République tchèque] ; Jan Roth [République tchèque]Source :
- Movement Disorders [ 0885-3185 ] ; 2011-01.
Descripteurs français
- Wicri :
- geographic : République tchèque.
English descriptors
- KwdEn :
- Adolescent, Adult, Age of Onset, Aged, CAG triplet, Czech Republic, Female, Gene Frequency, Genotype, Humans, Huntington Disease (genetics), Huntington's disease, Logistic Models, Male, Middle Aged, Nerve Tissue Proteins (genetics), Nuclear Proteins (genetics), Proportional Hazards Models, Trinucleotide Repeats (genetics), Young Adult, age at onset.
- 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. © 2010 Movement Disorder Society
Url:
DOI: 10.1002/mds.23436
Affiliations:
- Royaume-Uni, République tchèque
- Angleterre, Angleterre de l'Est, Bohême centrale
- Cambridge, Prague
- Université de Cambridge
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Le document en format XML
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Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-01">2011-01</date><biblScope unit="vol">26</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="125">125</biblScope><biblScope unit="page" to="129">129</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">0DE1F3F64D5CF0DE8A548E37E24640FA5AAF6B4D</idno><idno type="DOI">10.1002/mds.23436</idno><idno type="ArticleID">MDS23436</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Age of Onset</term><term>Aged</term><term>CAG triplet</term><term>Czech Republic</term><term>Female</term><term>Gene Frequency</term><term>Genotype</term><term>Humans</term><term>Huntington Disease (genetics)</term><term>Huntington's disease</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><term>age at onset</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><langUsage><language ident="en">en</language></langUsage></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. © 2010 Movement Disorder Society</div></front></TEI><affiliations><list><country><li>Royaume-Uni</li><li>République tchèque</li></country><region><li>Angleterre</li><li>Angleterre de l'Est</li><li>Bohême centrale</li></region><settlement><li>Cambridge</li><li>Prague</li></settlement><orgName><li>Université de Cambridge</li></orgName></list><tree><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><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="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="Židovská">Jana Židovská</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Stochl, Jan" sort="Stochl, Jan" uniqKey="Stochl J" first="Jan" last="Štochl">Jan Štochl</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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