PDF(Pubmed)
Abstract：
Chromatinopathies (CPs), a group of rare inborn defects characterized by chromatin state imbalance, have evolved from initially resembling Cornelia de Lange syndrome to encompass a wide array of genetic diseases with diverse clinical presentations. The CPs classification now includes human developmental disorders caused by germline mutations in epigenes, genes that regulate the epigenome. Recent advances in next-generation sequencing have enabled the association of 154 epigenes with CPs, revealing distinctive DNA methylation patterns known as episignatures.It has been shown that episignatures are unique for a particular CP or share similarities among specific CP subgroup. Consequently, these episignatures have emerged as promising biomarkers for diagnosing and treating CPs, differentiating subtypes, evaluating variants of unknown significance, and facilitating targeted therapies tailored to the underlying epigenetic dysregulation.The following review was conducted to collect, summarize, and analyze data regarding CPs in such aspects as clinical evaluation encompassing long-term patient care, underlying epigenetic changes, and innovative molecular and bioinformatic methodologies that have been devised for the assessment of CPs. We have also shed light on promising novel treatment options that have surfaced in recent research and presented a synthesis of ongoing clinical trials, contributing to the current understanding of the dynamic and evolving nature of CPs investigation.
摘要：
色谱病（CP），一组罕见的以染色质状态失衡为特征的先天性缺陷，已经从最初类似于CorneliadeLange综合征发展到涵盖具有不同临床表现的各种遗传疾病。CPs分类现在包括由表观基因中的种系突变引起的人类发育障碍，调节表观基因组的基因。下一代测序的最新进展使154个表观基因与CP相关联，揭示独特的DNA甲基化模式被称为表观标记。已经表明,表签名对于特定CP是唯一的,或者在特定CP子组中共享相似性。因此,这些表观特征已成为诊断和治疗CP的有前途的生物标志物，区分亚型，评估未知意义的变异，并促进针对潜在表观遗传失调的靶向治疗。进行了以下审查以收集，总结，并在包括长期患者护理的临床评估等方面分析有关CP的数据，潜在的表观遗传变化，以及为评估CP而设计的创新分子和生物信息学方法。我们还揭示了有希望的新型治疗方案，这些方案在最近的研究中浮出水面，并提出了正在进行的临床试验的综合。有助于当前对CP调查的动态和演变性质的理解。
