Diagnosis and Development, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC 3052, Australia.
Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC 3052, Australia.
Int J Mol Sci. 2020 Oct 19;21(20):7735. doi: 10.3390/ijms21207735.
Fragile X syndrome (FXS) is a leading single-gene cause of intellectual disability (ID) with autism features. This study analysed diagnostic and prognostic utility of the Fragile X-Related Epigenetic Element 2 DNA methylation (FREE2m) assessed by Methylation Specific-Quantitative Melt Analysis and the EpiTYPER system, in retrospectively retrieved newborn blood spots (NBS) and newly created dried blood spots (DBS) from 65 children with FXS (~2-17 years). A further 168 NBS from infants from the general population were used to establish control reference ranges, in both sexes. FREE2m analysis showed sensitivity and specificity approaching 100%. In FXS males, NBS FREE2m strongly correlated with intellectual functioning and autism features, however associations were not as strong for FXS females. Fragile X mental retardation 1 gene () mRNA levels in blood were correlated with FREE2m in both NBS and DBS, for both sexes. In females, DNAm was significantly increased at birth with a decrease in childhood. The findings support the use of FREE2m analysis in newborns for screening, diagnostic and prognostic testing in FXS.
脆性 X 综合征（FXS）是导致智力障碍（ID）和自闭症特征的主要单基因病因。本研究通过甲基化特异性定量熔解分析和 Epityper 系统分析了脆性 X 相关表观遗传元件 2 DNA 甲基化（FREE2m）的诊断和预后效用，该研究回顾性地分析了 65 名 FXS 儿童（~2-17 岁）的新生儿血斑（NBS）和新采集的干血斑（DBS）。还使用来自一般人群的 168 个 NBS 建立了控制参考范围，适用于男女两性。FREE2m 分析显示出接近 100%的灵敏度和特异性。在 FXS 男性中，NBS FREE2m 与智力功能和自闭症特征密切相关，但 FXS 女性的相关性不那么强。血液中脆性 X 智力低下 1 基因（）mRNA 水平与 NBS 和 DBS 中的 FREE2m 相关，适用于两性。在女性中，DNAm 在出生时显著增加，在儿童时期减少。这些发现支持在新生儿中使用 FREE2m 分析进行 FXS 的筛查、诊断和预后检测。
