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DNA methylation at birth predicts intellectual functioning and autism features in children with fragile x syndrome

journal contribution
posted on 15.12.2020, 01:53 by CM Kraan, Emma BakerEmma Baker, M Arpone, M Bui, L Ling, D Gamage, L Bretherton, C Rogers, MJ Field, TL Wotton, D Francis, MF Hunter, J Cohen, DJ Amor, DE Godler
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Fragile X syndrome (FXS) is a leading single-gene cause of intellectual disability (ID) with autism features. This study analysed diagnostic and prognostic utility of the Fragile X-Related Epigenetic Element 2 DNA methylation (FREE2m) assessed by Methylation Specific-Quantitative Melt Analysis and the EpiTYPER system, in retrospectively retrieved newborn blood spots (NBS) and newly created dried blood spots (DBS) from 65 children with FXS (~2–17 years). A further 168 NBS from infants from the general population were used to establish control reference ranges, in both sexes. FREE2m analysis showed sensitivity and specificity approaching 100%. In FXS males, NBS FREE2m strongly correlated with intellectual functioning and autism features, however associations were not as strong for FXS females. Fragile X mental retardation 1 gene (FMR1) mRNA levels in blood were correlated with FREE2m in both NBS and DBS, for both sexes. In females, DNAm was significantly increased at birth with a decrease in childhood. The findings support the use of FREE2m analysis in newborns for screening, diagnostic and prognostic testing in FXS.

Funding

This research was funded by The Victorian Government's Operational Infrastructure Support Program, Murdoch Children's Research Institute, Royal Children's Hospital Foundation, Martin and E.H. Flack Trust, Pierce Armstrong Trust, Financial Markets Foundation for Children (Australia) (FMFC; grant number: 2017-361), the National Health and Medical Research Council (NHMRC project grant numbers: 1049299 and 1103389 to D.E.G.; NHMRC Early Career fellowship project grant numbers. 1120561 to C.M.K.). D.E.G. salary was supported by the Next Generation Clinical Researchers Program-Career Development Fellowship Funded by the Medical Research Future Fund (grant number 1141334). Genetics of Learning Disability (GOLD) Service (M.J.F.). M.A. was supported by an Australian Postgraduate Award, the International Postgraduate Research Scholarships (IPRS) and the Research Training Program Fee offset scholarship funded by the Australian Government and awarded by the University of Melbourne, and in part by the Diagnosis and Development group of the Murdoch Children's Research Institute.

History

Publication Date

19/10/2020

Journal

International Journal of Molecular Sciences

Volume

21

Issue

20

Article Number

ARTN 7735

Pagination

18p.

Publisher

MDPI

ISSN

1422-0067

Rights Statement

The Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.