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首页> 外文期刊>Epigenetics & Chromatin >Identification of epigenetic signature associated with alpha thalassemia/mental retardation X-linked syndrome
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Identification of epigenetic signature associated with alpha thalassemia/mental retardation X-linked syndrome

机译：鉴定与α地中海贫血/智力低下X连锁综合征相关的表观遗传学特征

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Background Alpha thalassemia/mental retardation X-linked syndrome (ATR-X) is caused by a mutation at the chromatin regulator gene ATRX . 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 ATRX 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. 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 ATRX gene sequence variants of unknown significance.
机译：背景α地中海贫血/智力低下X连锁综合征（ATR-X）是由染色质调节基因ATRX突变引起的。尚未完全了解ATR-X病理学涉及的机制，但可能涉及表观遗传修饰。 ATRX与组蛋白H3和DNA甲基化的调节有关，而ATRX基因的突变可能导致下游表观遗传和转录作用。阐明在ATR-X中改变的潜在表观遗传机制将提供对该疾病的病理生物学的更好理解，并提供新颖的诊断生物标记。结果我们对18例ATR-X患者的外周血样本进行了全基因组DNA甲基化评估，并将其与210例对照进行了比较。我们证明了ATRX患者外周血中独特且高度特异性的DNA甲基化“表位”的证据，这通过靶向的亚硫酸氢盐测序实验得到了证实。尽管从基因组上讲，差异甲基化区域显示出在着丝粒和遥测染色体区域优先聚集的证据，ATRX具有与维持异染色质和基因组完整性有关的多种功能的区域。结论14个基因组位点中最显着的甲基化变化为该综合征提供了独特的表观遗传学特征，可用作高度敏感和特异性的诊断生物标志物，以支持ATR-X的诊断，特别是在表型复杂的患者和ATRX患者中意义未知的基因序列变体。

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