Identification of epigenetic signature associated with alpha thalassemia/mental retardation X-linked syndrome

Alpha thalassemia/mental retardation X-linked syndrome (ATR-X) is caused by a mutation at the chromatin regulator gene . The mechanisms involved in the ATR-X pathology are not completely understood, but may involve epigenetic modifications. ATRX has been linked to the regulation of histone H3 and DN...

Full description

Saved in:
Bibliographic Details
Published in:Epigenetics & chromatin 2017-03, Vol.10 (1), p.10-10, Article 10
Main Authors: Schenkel, Laila C, Kernohan, Kristin D, McBride, Arran, Reina, Ditta, Hodge, Amanda, Ainsworth, Peter J, Rodenhiser, David I, Pare, Guillaume, Bérubé, Nathalie G, Skinner, Cindy, Boycott, Kym M, Schwartz, Charles, Sadikovic, Bekim
Format: Article
Language:English
Subjects:
Adolescent
Adult
alpha-Thalassemia - genetics
alpha-Thalassemia - pathology
Biological markers
Child
Child, Preschool
Chromatin
Chromosomes
CpG Islands
Deoxyribonucleic acid
DNA
DNA - chemistry
DNA - isolation & purification
DNA - metabolism
DNA Methylation
Epigenesis, Genetic
Epigenetic inheritance
Epigenetics
Gene expression
Gene regulation
Genetic aspects
Genomes
Genomics
Genotype
Humans
Identification
Infant
Intellectual disabilities
Leukemia
Male
Mental Retardation, X-Linked - genetics
Mental Retardation, X-Linked - pathology
Methylation
Middle Aged
Mutation
Nucleotide sequence
Promoter Regions, Genetic
Proteins
Sequence Analysis, DNA
Thalassemia
X-linked Nuclear Protein - genetics
X-linked Nuclear Protein - metabolism
Young Adult
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Alpha thalassemia/mental retardation X-linked syndrome (ATR-X) is caused by a mutation at the chromatin regulator gene . The mechanisms involved in the ATR-X pathology are not completely understood, but may involve epigenetic modifications. ATRX has been linked to the regulation of histone H3 and DNA methylation, while mutations in the gene may lead to the downstream epigenetic and transcriptional effects. Elucidating the underlying epigenetic mechanisms altered in ATR-X will provide a better understanding about the pathobiology of this disease, as well as provide novel diagnostic biomarkers. 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. 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 gene sequence variants of unknown significance.
ISSN:1756-8935
1756-8935
DOI:10.1186/s13072-017-0118-4