Microdeletions in the human H19 DMR result in loss of IGF2 imprinting and Beckwith-Wiedemann syndrome
Microdeletions in the human H19 DMR result in loss of IGF2 imprinting and Beckwith-Wiedemann syndrome
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DOI：
10.1038/ng1410
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发表时间：
2004-09-01
期刊：
影响因子：
30.8
通讯作者：
Riccio, A
中科院分区：
文献类型：
--
作者：
Sparago, A;Cerrato, F;Riccio, A
过度生长和肿瘤相关的Beckwith-Wiedemann综合征是由染色体11p15.5上的印记基因失调引起的。在这里，我们表明，在H19差异甲基化区域（DMR），取消两个CTCF靶位点的遗传性微缺失导致这种疾病。缺失的母体传递导致H19 DMR的超甲基化、双等位基因IGF 2表达、H19沉默和Beckwith-Wiedemann综合征，表明IGF 2-H19印迹控制元件的功能丧失。
The overgrowth- and tumor-associated Beckwith-Wiedemann syndrome results from dysregulation of imprinted genes on chromosome 11p15.5. Here we show that inherited microdeletions in the H19 differentially methylated region (DMR) that abolish two CTCF target sites cause this disease. Maternal transmission of the deletions results in hypermethylation of the H19 DMR, biallelic IGF2 expression, H19 silencing and Beckwith-Wiedemann syndrome, indicative of loss of function of the IGF2-H19 imprinting control element.