Analysis of genetic defects in the 11p15.5 region in Russell-Silver syndrome
10.3969/j.issn.1000-3606.2018.03.012
- VernacularTitle:Russell-Silver综合征11p15.5区域遗传缺陷分析
- Author:
Chaoran XIA
1
,
2
;
Yongchen YANG
;
Wuhen XU
;
Zhaoning LU
;
Wei WANG
Author Information
1. 上海交通大学附属儿童医院 上海市儿童医院 上海交通大学医学遗传研究所
2. 卫生部医学胚胎分子生物学重点实验室 上海市胚胎与生殖工程重点实验室
- Keywords:
Russell-Silver syndrome;
methylation aberration;
11p15.5;
genomic imprinting
- From:
Journal of Clinical Pediatrics
2018;36(3):210-215
- CountryChina
- Language:Chinese
-
Abstract:
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.
