目的　探讨Russell-Silver综合征（RSS）发病机制。方法　采集6例男性，年龄6~8岁的临床表型疑似RSS患儿， 以及2例患儿父母、 5例健康男性儿童的外周血2 mL，分离单个核细胞并提取基因组DNA，应用焦磷酸测序技术进行分析， 检测染色体11p15.5上印记基因控制区域（ICR） 1的H19基因的甲基化水平。应用甲基化特异性多重连接探针扩增技术 （MS-MLPA）对1例焦磷酸测序结果阳性且为RSS患儿的甲基化水平进行验证分析并对相应区域的基因拷贝数进行检测。 结果　焦磷酸测序结果显示， 6例患儿在H19-差异甲基化区域（DMR）的6个CpG位点的甲基化率为11%~29%；患儿父 母及正常对照组对应位点的甲基化率为44%~59%。焦磷酸测序结果阳性的1例患儿对应的MS-MLPA结果显示，H19基 因的4个位点甲基化率在10%左右，明显低于正常水平。KCNQ1OT1基因的4个位点甲基化率约为50%，在正常范围内。 所测样本的基因拷贝数均在正常范围内。结论　RSS患儿的ICR1的H19-DMR存在甲基化水平异常。

　Objective　To explore the pathogenesis of Russell-Silver syndrome (RSS). Methods　Two milliliter peripheral blood samples were collected from 6 male patients aged 6 to 8 years with suspected RSS phenotype, the parents of 2 patients and 5 healthy boys. Mononuclear cells were isolated and genomic DNA was extracted. The methylation level of the H19 imprinting control region (ICR) 1 on chromosome 11p15.5 was detected by pyrosequencing. The methylation status and the copy number variation in the corresponding region of one RSS patient with positive results by pyrosequencing were analysed by methylation-specific multiplex-ligation-dependent probe amplification assay (MS-MLPA). Results　Pyrosequencing analysis revealed that the methylation rates on the 6 CpG targeting sites in H19 differentially methylated region (DMR) in the 6 RSS patients were about 11%~29%, which were significantly lower than those in their parents and normal controls (44%~59%). The MS-MLPA results of one patient with positive pyrosequencing showed that the methylation rates of 4 sites in H19-DMR were about 10%, which was obviously lower than the normal level. The methylation rates of the 4 sites in KCNQ1OT1 gene were about 50%, which was in the normal range. The copy number variations from all samples detected were in the normal range. Conclusion　There is methylation aberration of H19-DMR in ICR1 in children with RSS.