Intragenic DNA methylation in buccal epithelial cells and intellectual functioning in a paediatric cohort of males with fragile X
Author
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Arpone, Marta
Author
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Baker, Emma K.
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Bretherton, Lesley
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Bui, Minh
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Li, Xin
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Whitaker, Simon
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Dissanayake, Cheryl
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Cohen, Jonathan
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Hickerton, Chriselle
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Rogers, Carolyn
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Field, Mike
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Elliott, Justine
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Aliaga, Solange M.
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Ling, Ling
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Francis, David
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Hearps, Stephen J. C.
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Hunter, Matthew F.
Author
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Amor, David J.
Author
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Godler, David E.
Admission date
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2018-07-31T16:36:29Z
Available date
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2018-07-31T16:36:29Z
Publication date
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2018
Cita de ítem
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Scientific Reports (2018) 8: 3644
es_ES
Identifier
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10.1038/s41598-018-21990-x
Identifier
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https://repositorio.uchile.cl/handle/2250/150491
Abstract
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Increased intragenic DNA methylation of the Fragile X Related Epigenetic Element 2 (FREE2) in blood has been correlated with lower intellectual functioning in females with fragile X syndrome (FXS). This study explored these relationships in a paediatric cohort of males with FXS using Buccal Epithelial Cells (BEC). BEC were collected from 25 males with FXS, aged 3 to 17 years and 19 age-matched male controls without FXS. Methylation of 9 CpG sites within the FREE2 region was examined using the EpiTYPER approach. Full Scale IQ (FSIQ) scores of males with FXS were corrected for floor effect using the Whitaker and Gordon (WG) extrapolation method. Compared to controls, children with FXS had significant higher methylation levels for all CpG sites examined (p < 3.3 x 10(-7)), and within the FXS group, lower FSIQ (WG corrected) was associated with higher levels of DNA methylation, with the strongest relationship found for CpG sites within FMR1 intron 1 (p < 5.6 x 10(-5)). Applying the WG method to the FXS cohort unmasked significant epi-genotype-phenotype relationships. These results extend previous evidence in blood to BEC and demonstrate FREE2 DNA methylation to be a sensitive epigenetic biomarker significantly associated with the variability in intellectual functioning in FXS.
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Patrocinador
dc.description.sponsorship
Victorian Government's Operational Infrastructure Support Program
Murdoch Children's Research Institute
Royal Children's Hospital Foundation
Martin & E.H. Flack Trust
Pierce Armstrong Trust
Financial Markets Foundation for Children (Australia) (FMFC)
2017-361
National Health and Medical Research Council (NHMRC)
1017263
104299
1103389
NHMRC
1017263
104299
Next Generation Clinical Researchers Program - Career Development Fellowship Funded from the Medical Research Future Fund
1141334
International Postgraduate Research Scholarships (IPRS)
Research Training Program Fee offset scholarship - Australian Government
University of Melbourne
Cyto-molecular Diagnostics Research group of the Murdoch Children's Research Institute
CONICYT
Chile's National Commission for Scientific and Technological Research