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

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 wit

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Additional file 2: Table S1. ATR-X methylation; significant regions detected by methylation array in ATR-X patients (n = 17) compared with controls (n = 210) using cutoff of probes >3, estimate >15%, F value >50, p value <0.01

MOESM1 of Identification of epigenetic signature associated with alpha thalassemia/mental retardation X-linked syndrome

Additional file 1: Figure S1. Methylation string diagrams of significantly altered regions in ATR-X patients and controls. Bisulfite mutagenesis and sequencing analysis was performed in approximately 20 alleles from each sample, and individual alleles are represented as a string of CpGs. The total average methylation for each sample is indicated. Unmethylated CpGs are represented as empty circles, and methylated CpGs as filled circles