PARENTAL ALLELE-SPECIFIC METHYLATION OF THE HUMAN INSULIN-LIKE GROWTHFACTOR-II GENE AND BECKWITH-WIEDEMANN SYNDROME

In an attempt to elucidate the role of methylation in parental imprint ing at the IGF-II gene locus, for which imprinting has already been de scribed in the mouse' we undertook an allele specific methylation stud y of the human IGF-II gene (mapped to 11p15.5) in a control population and in patients with Beckwith-Wiedemann syndrome. In control leucocyt e DNA (16 unrelated adults and eight families), the maternal allele of the IGF-II gene was specifically hypomethylated, whereas no such alle le specific methylation was found for either the insulin or the calcit onin genes which are located in 11p15.5 and 11p15.1, respectively. Fur thermore, the IGF-II gene specific hypomethylation was localised on th e 5' portion of exon 9. In the patients with Beckwith-Wiedemann syndro me in which the IGF-II gene is thought to be involved and where patern al isodisomy has been described, hypomethylation of the maternal allel e was conserved in leucocyte DNA, but abnormal methylation was detecte d in malformed tissues where the paternal allele was also demethylated . Some specific mechanism linked to methylation therefore seems to be involved in the pathogenesis of Beckwith-Wiedemann syndrome.