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© 1994 Oxford University Press
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Allelic methylation of H19 and IGF2 in the Beckwith — Wiedemann syndrome
Laboratory of Developmental Genetics and Imprinting, The Babraham Institute Cambridge CB2 4AT 1Department of Pathology and Microbiology, School of Medical Sciences, University Walk Bristol BS8 1TD 2Motecular Genetics Laboratory, Addenbrooke's NHS Trust Cambridge 3Institute of Child Health, Royal Hospital for Sick Children, St Michael's Hill Bristol BS2 8BJ 4Department of Clinical Genetics, Addenbrooke's NHS Trust Cambridge 5Cambridge University, Department of Pathology Tennis Court Road, Cambridge, UK
* To whom correspondence should be addressed
Received March 30, 1994; Accepted May 24, 1994
Beckwith-Wiedemann syndrome (BWS) Is a congenital overgrowth syndrome with associated embryonal tumours. Most BWS cases are sporadic but familial cases occur In 15% of patients and in these there is linkage to chromosome 11p15. In addition, a small number of patients have cytogenetic abnormalities involving chromosome 11 p15. Approximately 20% of sporadic BWS patients have uniparental paternal dlsomy (UPD) of chromosome 11 p15. This finding together with the observation that penetrance in familial cases depends on parental transmission, suggests that the gene(s) for BWS are imprinted. The recent demonstration of blallellc expression of the otherwise maternally imprinted IGF2 gene In some BWS patients implicates excess IGF2 expression in the disease. Here we have analysed the allele-specific methylation patterns In the IGF2 gene and in the neighbouring and reciprocally Imprinted H19 gene in a group of 42 BWS patients, 10 of which were mosaic UPD cases. We found that allelic methylation of both genes was normal in all non-UPD cases, with the paternal allele being methylated, and was Increased In UPD cases in proportion with the disomlc lineage. These findings suggest that sporadic BWS is not associated with a general alteration of methylation imprinting of the IGF2 and H19 genes. The methylation assay used in this study thus also offers a simple and reliable diagnostic test of UPD for 11p15.5. An unexpected finding was a distortion of the frequency of AvaU alleles at the IGF2 locus exclusively in UPD BWS cases (P < 0.001). This further Implicates the IGF2 gene in aspects of the BWS phenotype.
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