Genes that are subject to genomic imprinting are exclusively expressed from either maternal or paternal chromosomes but not both during normal development.  Sometimes, mutations or defects in epigenetic regulatory mechanisms disrupt normal imprinted gene expression. Abnormal imprinted gene expression can give rise to rare developmental growth disorders such as Beckwith-Wiedemann syndrome (BWS) and Russell-Silver syndrome (RSS).  While disease severity varies over a wide spectrum for these syndromes, tissue from patients with BWS and RSS frequently exhibit “phenotypic mosaicism” a phenomenon in which cells from different organs exhibit dysregulated imprinted gene regulation to varying degrees.

Researchers at the Center for Childhood Cancer Research Center are studying the underlying cellular and molecular mechanisms that contribute to the epigenetic mosaicism characteristic of patients with RSS and BWS.  To accomplish this, researchers at the Childhood Cancer Research Center in collaboration with researchers at the University of Pennsylvania are applying a new fluorescence hybridization technique that measures allele-specific expression in single cells from murine models of RSS. Results from these experiments revealed that imprinting disorders can display striking single-cell heterogeneity in molecular phenotype and that this heterogeneity may underlie the epigenetic mosaicism characteristic of human imprinting gene disorders.

Additional experiments are underway to determine whether or not this assay is applicable to human cell lines derived from patients with BWS, RSS and other human imprinting gene disorders.