DISRUPTION OF INSULIN-LIKE GROWTH FACTOR-II IMPRINTING IN BECKWITH-WIEDEMANN SYNDROME

To study insulin-like growth factor 2 (IGF2) imprinting in BWS (Beckwi th-Wiedemann syndrome, an overgrowth syndrome associated with Wilms an d other embryonal tumours), we examined allele-specific expression usi ng an ApaI polymorphism in the 3' untranslated region of IGF2. Four of six BWS fibroblast strains demonstrated biallelic expression, as did the tongue tissue from one of these patients. Paternal heterodisomy wa s excluded for all BWS patients with biallelic expression, suggesting strongly that the BWS phenotype in some patients involves disruption o f IGF2 imprinting. Constitutional loss of IGF2 imprinting in a subgrou p of our BWS patients, and recent reports of loss of imprinting in spo radic Wilms tumour, further strengthens the view that IGF2 overexpress ion plays an important role in somatic overgrowth and the development of embryonal tumours.