Imprinting mutation in the BeckwithWiedemann syndrome leads to biallelic IGF2 expression through an H19 independent pathway

The Beckwith–Wiedemann syndrome (BWS) is geneti-cally linked to chromosome 11p15.5, and a variety of observations suggest that deregulation of imprinted genes in this region is causally involved in the patho-genesis of the disease. It has been shown that in some patients without cytogenetic abnormalities the other-wise repressed maternal copy of the insulin-like growth factor 2 (IGF2) gene is expressed, leading to biallelic expression of IGF2. In some of these cases, this is accompanied by repression and DNA methyla-tion of the maternal (otherwise active) copy of the neighbouring H19 gene. Hence, it is attractive to think that mutations may interfere with some aspect of H19 imprinting, thus leading to an inactive maternal allele, and indirectly to activation of the maternal IGF2 allel