Title

Identification of Epigenetic Signature Associated With Alpha Thalassemia/Mental Retardation X-linked Syndrome

Authors

Laila C Schenkel, Western University
Kristin D Kernohan, University of Ottawa
Arran McBride, University of Ottawa
Ditta Reina, McMaster University
Amanda Hodge, McMaster University
Peter J Ainsworth, Western University
David I Rodenhiser, Western University
Guillaume Pare, McMaster University
Nathalie G Bérubé, Western University
Cindy Skinner, Greenwood Genetic Center
Kym M Boycott, University of Ottawa
Charles Schwartz, Greenwood Genetic Center
Bekim Sadikovic, Western University

Document Type

Article

Publication Date

1-2017

Journal

Epigenetics Chromatin

Volume

10

URL with Digital Object Identifier

https://doi.org/10.1186/s13072-017-0118-4

Abstract

BACKGROUND: Alpha thalassemia/mental retardation X-linked syndrome (ATR-X) is caused by a mutation at the chromatin regulator gene

RESULTS: We performed genome-wide DNA methylation assessment of the peripheral blood samples from 18 patients with ATR-X and compared it to 210 controls. We demonstrated the evidence of a unique and highly specific DNA methylation "epi-signature" in the peripheral blood of ATRX patients, which was corroborated by targeted bisulfite sequencing experiments. Although genomically represented, differentially methylated regions showed evidence of preferential clustering in pericentromeric and telometric chromosomal regions, areas where ATRX has multiple functions related to maintenance of heterochromatin and genomic integrity.

CONCLUSION: Most significant methylation changes in the 14 genomic loci provide a unique epigenetic signature for this syndrome that may be used as a highly sensitive and specific diagnostic biomarker to support the diagnosis of ATR-X, particularly in patients with phenotypic complexity and in patients with

Notes

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