Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0042617
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dc.titleGlutamine repeat variants in human RUNX2 associated with decreased femoral neck BMD, broadband ultrasound attenuation and target gene transactivation
dc.contributor.authorMorrison N.A.
dc.contributor.authorStephens A.A.
dc.contributor.authorOsato M.
dc.contributor.authorPolly P.
dc.contributor.authorTan T.C.
dc.contributor.authorYamashita N.
dc.contributor.authorDoecke J.D.
dc.contributor.authorPasco J.
dc.contributor.authorFozzard N.
dc.contributor.authorJones G.
dc.contributor.authorRalston S.H.
dc.contributor.authorSambrook P.N.
dc.contributor.authorPrince R.L.
dc.contributor.authorNicholson G.C.
dc.date.accessioned2020-03-18T05:44:43Z
dc.date.available2020-03-18T05:44:43Z
dc.date.issued2012
dc.identifier.citationMorrison N.A., Stephens A.A., Osato M., Polly P., Tan T.C., Yamashita N., Doecke J.D., Pasco J., Fozzard N., Jones G., Ralston S.H., Sambrook P.N., Prince R.L., Nicholson G.C. (2012). Glutamine repeat variants in human RUNX2 associated with decreased femoral neck BMD, broadband ultrasound attenuation and target gene transactivation. PLoS ONE 7 (8) : e42617. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0042617
dc.identifier.issn19326203
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/165568
dc.description.abstractRUNX2 is an essential transcription factor required for skeletal development and cartilage formation. Haploinsufficiency of RUNX2 leads to cleidocranial displaysia (CCD) a skeletal disorder characterised by gross dysgenesis of bones particularly those derived from intramembranous bone formation. A notable feature of the RUNX2 protein is the polyglutamine and polyalanine (23Q/17A) domain coded by a repeat sequence. Since none of the known mutations causing CCD characterised to date map in the glutamine repeat region, we hypothesised that Q-repeat mutations may be related to a more subtle bone phenotype. We screened subjects derived from four normal populations for Q-repeat variants. A total of 22 subjects were identified who were heterozygous for a wild type allele and a Q-repeat variant allele: (15Q, 16Q, 18Q and 30Q). Although not every subject had data for all measures, Q-repeat variants had a significant deficit in BMD with an average decrease of 0.7SD measured over 12 BMD-related parameters (p = 0.005). Femoral neck BMD was measured in all subjects (-0.6SD, p = 0.0007). The transactivation function of RUNX2 was determined for 16Q and 30Q alleles using a reporter gene assay. 16Q and 30Q alleles displayed significantly lower transactivation function compared to wild type (23Q). Our analysis has identified novel Q-repeat mutations that occur at a collective frequency of about 0.4%. These mutations significantly alter BMD and display impaired transactivation function, introducing a new class of functionally relevant RUNX2 mutants. © 2012 Morrison et al.
dc.publisherPublic Library of Science
dc.sourceUnpaywall 20200320
dc.subjectpolyglutamine
dc.subjecttranscription factor RUNX2
dc.subjectvitamin D receptor
dc.subjectadult
dc.subjectaged
dc.subjectallele
dc.subjectarticle
dc.subjectbone densitometry
dc.subjectbone density
dc.subjectfemale
dc.subjectfemur neck
dc.subjectgene frequency
dc.subjectgene function
dc.subjectgene mutation
dc.subjectgene targeting
dc.subjectgenetic association
dc.subjectgenetic variability
dc.subjecthuman
dc.subjectmutational analysis
dc.subjectmutator gene
dc.subjectRunx2 gene
dc.subjecttransactivation
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectAnimals
dc.subjectBone Density
dc.subjectCleidocranial Dysplasia
dc.subjectCore Binding Factor Alpha 1 Subunit
dc.subjectFemale
dc.subjectFemoral Neck Fractures
dc.subjectFemur Neck
dc.subjectGenetic Predisposition to Disease
dc.subjectGlutamine
dc.subjectHEK293 Cells
dc.subjectHumans
dc.subjectMice
dc.subjectMonte Carlo Method
dc.subjectMutation
dc.subjectNIH 3T3 Cells
dc.subjectReceptors, Calcitriol
dc.subjectRepetitive Sequences, Amino Acid
dc.subjectTranscriptional Activation
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.description.doi10.1371/journal.pone.0042617
dc.description.sourcetitlePLoS ONE
dc.description.volume7
dc.description.issue8
dc.description.pagee42617
dc.published.statePublished
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