Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0042617
Title: Glutamine repeat variants in human RUNX2 associated with decreased femoral neck BMD, broadband ultrasound attenuation and target gene transactivation
Authors: Morrison 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.
Keywords: polyglutamine
transcription factor RUNX2
vitamin D receptor
adult
aged
allele
article
bone densitometry
bone density
female
femur neck
gene frequency
gene function
gene mutation
gene targeting
genetic association
genetic variability
human
mutational analysis
mutator gene
Runx2 gene
transactivation
Adult
Aged
Aged, 80 and over
Animals
Bone Density
Cleidocranial Dysplasia
Core Binding Factor Alpha 1 Subunit
Female
Femoral Neck Fractures
Femur Neck
Genetic Predisposition to Disease
Glutamine
HEK293 Cells
Humans
Mice
Monte Carlo Method
Mutation
NIH 3T3 Cells
Receptors, Calcitriol
Repetitive Sequences, Amino Acid
Transcriptional Activation
Issue Date: 2012
Publisher: Public Library of Science
Citation: Morrison 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
Abstract: RUNX2 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.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/165568
ISSN: 19326203
DOI: 10.1371/journal.pone.0042617
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1371_journal_pone_0042617.pdf444.13 kBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

7
checked on Oct 19, 2020

Page view(s)

51
checked on Oct 16, 2020

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.