Academic Unit of Genetic Medicine, School of Medicine, University of Southampton, Princess Anne Hospital, Southampton, UK.
Eur J Hum Genet. 2010 Jun;18(6):648-55. doi: 10.1038/ejhg.2009.246. Epub 2010 Jan 27.
This study was an investigation of 79 patients referred to the Wessex Regional Genetics Laboratory with suspected Russell-Silver Syndrome or unexplained short stature/intra uterine growth restriction, warranting genetic investigation. Methylation status was analysed at target sequences within eleven imprinted loci (PLAGL1, IGF2R, PEG10, MEST1, GRB10, KCNQ1OT1, H19, IGF2P0, DLK1, PEG3, NESPAS). Thirty seven percent (37%) (29 of 79) of samples were shown to have a methylation abnormality. The commonest finding was a loss of methylation at H19 (23 of 29), as previously reported in Russell-Silver Syndrome. In addition, four of these patients had methylation anomalies at other loci, of whom two showed hypomethylation of multiple imprinted loci, and two showed a complete gain of methylation at IGF2R. This latter finding was also present in five other patients who did not have demonstrable changes at H19. In total, 7 of 79 patients showed a gain of methylation at IGF2R and this was significantly different from a normal control population of 267 individuals (P=0.002). This study in patients with growth restriction shows the importance of widening the epigenetic investigation to include multiple imprinted loci and highlights potential involvement of the IGF2R locus.
这项研究调查了 79 名被转介到威塞克斯地区遗传学实验室的患者，这些患者疑似患有 Russell-Silver 综合征或原因不明的身材矮小/宫内生长受限，需要进行基因检查。在 11 个印迹基因座（PLAGL1、IGF2R、PEG10、MEST1、GRB10、KCNQ1OT1、H19、IGF2P0、DLK1、PEG3、NESPAS）内的目标序列分析了甲基化状态。结果显示，37%（79 例中的 29 例）的样本存在甲基化异常。最常见的发现是 H19 失去甲基化（29 例中的 23 例），如先前在 Russell-Silver 综合征中报道的那样。此外，其中 4 名患者在其他基因座存在甲基化异常，其中 2 名患者多个印迹基因座呈低甲基化，2 名患者 IGF2R 呈完全甲基化获得。另外 5 名患者也存在 IGF2R 完全甲基化获得的情况，而 H19 没有明显变化。总共有 7 例患者 IGF2R 获得甲基化，与 267 例正常对照人群相比差异有统计学意义（P=0.002）。这项对生长受限患者的研究表明，扩大表观遗传学检查范围，包括多个印迹基因座的重要性，并强调了 IGF2R 基因座的潜在参与。
