Sparago Angela, Cerrato Flavia, Vernucci Maria, Ferrero Giovanni Battista, Silengo Margherita Cirillo, Riccio Andrea
Dipartimento di Scienze Ambientali, Seconda Università di Napoli, via Vivaldi 43, 81100 Caserta, Italy.
Nat Genet. 2004 Sep;36(9):958-60. doi: 10.1038/ng1410. Epub 2004 Aug 15.
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.
与过度生长和肿瘤相关的贝克威思-维德曼综合征是由11号染色体p15.5上印记基因的失调引起的。我们在此表明，H19差异甲基化区域（DMR）中的遗传性微缺失消除了两个CTCF靶位点，从而导致了这种疾病。这些缺失的母系传递导致H19 DMR的高甲基化、IGF2双等位基因表达、H19沉默和贝克威思-维德曼综合征，表明IGF2-H19印记控制元件功能丧失。
