LaSalle Janine M
Department of Medical Microbiology and Immunology, Perinatal Origins of Disparities Center, MIND Institute, Genome Center, Environmental Health Sciences Center, University of California Davis, One Shields Ave., Davis, CA, 95616, USA.
J Neurodev Disord. 2025 Feb 19;17(1):10. doi: 10.1186/s11689-025-09598-5.
Epigenetic mechanisms, including DNA methylation, act at the interface of genes and environment by allowing a static genome to respond and adapt to a dynamic environment during the lifespan of an individual. Genome-wide DNA methylation analyses on a wide range of human biospecimens are beginning to identify epigenetic biomarkers that can predict risk of intellectual/developmental disabilities (IDD). DNA methylation-based epigenetic signatures are becoming clinically useful in categorizing benign from pathogenic genetic variants following exome sequencing. While DNA methylation marks differ by tissue source, recent studies have shown that accessible perinatal tissues, such as placenta, cord blood, newborn blood spots, and cell free DNA may serve as accessible surrogate tissues for testing epigenetic biomarkers relevant to understanding genetic, environmental, and gene by environment interactions on the developing brain. These DNA methylation signatures may also provide important information about the biological pathways that become dysregulated prior to disease progression that could be used to develop early pharmacological interventions. Future applications could involve preventative screenings using DNA methylation biomarkers during pregnancy or the newborn period for IDDs and other neurodevelopmental disorders. DNA methylation biomarkers in adolescence and adulthood are also likely to be clinically useful for tracking biological aging or co-occurring health conditions that develop across the lifespan. In conclusion, DNA methylation biomarkers are expected to become more common in clinical diagnoses of IDD, to improve understanding of complex IDD etiologies, to improve endpoints for clinical trials, and to monitor potential health concerns for individuals with IDD as they age.
表观遗传机制，包括DNA甲基化，通过使静态基因组在个体寿命期间对动态环境做出反应和适应，在基因与环境的界面发挥作用。对广泛的人类生物样本进行全基因组DNA甲基化分析，开始识别出可预测智力/发育障碍（IDD）风险的表观遗传生物标志物。基于DNA甲基化的表观遗传特征在对全外显子测序后的良性和致病基因变异进行分类方面正变得具有临床实用性。虽然DNA甲基化标记因组织来源而异，但最近的研究表明，可获取的围产期组织，如胎盘、脐带血、新生儿血斑和游离DNA，可作为可获取的替代组织，用于测试与理解发育中的大脑上的遗传、环境以及基因与环境相互作用相关的表观遗传生物标志物。这些DNA甲基化特征还可能提供有关在疾病进展之前失调的生物学途径的重要信息，可用于开发早期药物干预措施。未来的应用可能包括在孕期或新生儿期使用DNA甲基化生物标志物对IDD和其他神经发育障碍进行预防性筛查。青少年期和成年期的DNA甲基化生物标志物在追踪生物衰老或一生中出现的并发健康状况方面也可能具有临床实用性。总之，预计DNA甲基化生物标志物在IDD的临床诊断中会变得更加普遍，以增进对复杂IDD病因的理解，改善临床试验的终点，并监测IDD个体随着年龄增长可能出现的健康问题。
