Artículo de revista
Intragenic DNA methylation in buccal epithelial cells and intellectual functioning in a paediatric cohort of males with fragile X
Fecha
2018Registro en:
Scientific Reports (2018) 8: 3644
10.1038/s41598-018-21990-x
Autor
Arpone, Marta
Baker, Emma K.
Bretherton, Lesley
Bui, Minh
Li, Xin
Whitaker, Simon
Dissanayake, Cheryl
Cohen, Jonathan
Hickerton, Chriselle
Rogers, Carolyn
Field, Mike
Elliott, Justine
Aliaga, Solange M.
Ling, Ling
Francis, David
Hearps, Stephen J. C.
Hunter, Matthew F.
Amor, David J.
Godler, David E.
Institución
Resumen
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.