Proportion of cells with paternal 11p15 uniparental disomy correlates withorgan enlargement in Wiedemann-Beckwith syndrome

"Genetic mosaicism" describes the presence of two or more populations of ce lls within a single individual that differ in their genomic constitution. A lthough the occurrence of asymmetric overgrowth in Wiedemann-Beckwith syndr ome (WBS) suggests that mosaicism has some role in the WBS phenotype, no di rect evidence for this has been published. WBS is a congenital overgrowth s yndrome with variable phenotype linked to the imprinted gene cluster on chr omosome region 11p15. We have performed a molecular survey of multiple orga ns and tissues in a case of WBS with a high degree of mosaic paternal 11p15 uniparental disomy (UPD), The organs most severely affected were those wit h the highest percentage of cells with UPD, In particular there was a strik ing difference in the degree of mosaicism for 11p15 UPD between the extreme ly enlarged left adrenal and non-enlarged right adrenal gland, This result indicates that the proportion of paternal 11p15 UPD cells correlates with t he tissue phenotype of WBS. Our results suggest that high proportions of ab normal cells result from a combination of stochastic events and cell select ion. Mosaicism may explain the variable phenotypes including hemihyperplasi a and predisposition to childhood cancers in WBS patients. Am. J, Med. Gene t, 92:111-116, 2000, (C) 2000 Wiley-Liss, Inc.