Intragenic DNA Methylation in Buccal Epithelial Cells and Intellectual Functioning in a Paediatric Cohort of Males with Fragile X

Overview

Journal Sci Rep

Specialty Science

Date 2018 Feb 28

PMID 29483611

Citations 12

Authors

Marta Arpone

Emma K Baker

Lesley Bretherton

Minh Bui

Xin Li

Simon Whitaker

Cheryl Dissanayake

Jonathan Cohen

Chriselle Hickerton

Carolyn Rogers

Mike Field

Justine Elliott

Solange M Aliaga

Ling Ling

David Francis

Stephen J C Hearps

Matthew F Hunter

David J Amor

David E Godler

Affiliations

Soon will be listed here.

Abstract

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 × 10), 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 × 10). 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.

Citing Articles

Tissue mosaicism, FMR1 expression and intellectual functioning in males with fragile X syndrome.

Baker E, Arpone M, Bui M, Kraan C, Ling L, Francis D Am J Med Genet A. 2022; 191(2):357-369.

PMID: 36349505 PMC: 10952635. DOI: 10.1002/ajmg.a.63027.

The Cost of Raising Individuals with Fragile X or Chromosome 15 Imprinting Disorders in Australia.

Baker E, Arora S, Amor D, Date P, Cross M, OBrien J J Autism Dev Disord. 2021; 53(4):1682-1692.

PMID: 34292487 DOI: 10.1007/s10803-021-05193-4.

Detection of Cryptic Fragile X Full Mutation Alleles by Southern Blot in a Female and Her Foetal DNA via Chorionic Villus Sampling, Complicated by Mosaicism for 45,X0/46,XX/47,XXX.

Pandelache A, Francis D, Oertel R, Dickson R, Sachdev R, Ling L Genes (Basel). 2021; 12(6).

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Relationships between UBE3A and SNORD116 expression and features of autism in chromosome 15 imprinting disorders.

Baker E, Butler M, Hartin S, Ling L, Bui M, Francis D Transl Psychiatry. 2020; 10(1):362.

PMID: 33116122 PMC: 7595031. DOI: 10.1038/s41398-020-01034-7.

DNA Methylation at Birth Predicts Intellectual Functioning and Autism Features in Children with Fragile X Syndrome.

Kraan C, Baker E, Arpone M, Bui M, Ling L, Gamage D Int J Mol Sci. 2020; 21(20).

PMID: 33086711 PMC: 7589848. DOI: 10.3390/ijms21207735.

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