Silver-Russell Syndrome （SRS）是一种罕见的遗传异质性疾病，其主要临床特征是严重的宫内和生后生长发育迟缓。相关基因位点甲基化调控异常是SRS发病的主要机制。本课题组前期研究发现约37.5%患者病因不明，采用全基因组甲基化芯片对这部分患者进行检测，结果发现OSBPL5基因内5’端的cg25963939位点低甲基化与SRS的发病显著相关，并用焦磷酸测序得到了证实。虽然已知OSBPL5基因在胚胎的生长发育中起重要作用，但目前对于该基因甲基化状态与SRS发生的关系尚未明确。因此，本课题拟通过体内和体外功能学实验进一步确认和研究OSBPL5基因及cg25963939对应调控元件在SRS发生中的作用及相应分子机制。本课题的完成预期可阐明OSBPL5基因低甲基化在生长发育中的作用，明确该基因组区域是否为SRS的致病位点，为SRS的分子诊断提供新的实验和理论依据。

Silver-Russell Syndrome (SRS) is a rare disease with high genetic heterogeneity. Its main features were severe intrauterine and postnatal growth retardation. The methylation abnormal of related gene is a major mechanism in the pathogenesis of SRS.Our previous studies showed about 37.5% of the patients with unknown etiology.We found low methylation of 5 'end of cg25963939 of OSBPL5（oxysterol binding protein like 5）gene by whole genome DNA methylation chip and confirmed it having close relation to the SRS onset with pyrosequencing. Although the OSBPL5 gene plays an important role in the growth of the embryo, the relationship between SRS and methylation of OSBPL5 gene are not clear. Therefore, this research intends to further confirm the gene and the corresponding regulatory element sequence of cg25963939 on the molecular regulating mechanism of SRS through experiments in vivo and in vitro. It also elucidates the affection of OSBPL5 gene methylation in growth and development, and at last, clarify whether OSBPL5 gene as a candidate gene of SRS to provide new experimental and theoretical basis for the molecular diagnosis.