Genomic imprinting is a particularly attractive example of epigenetic regulation leading to the parental-origin-specific expression of genes. In several ways, the 11p15 imprinted region is an exemplary model for regulation of genomic imprinting. The two imprinted domains are controlled by imprinting control regions (ICRs) which carry opposite germ line imprints and they are regulated by two major mechanisms of imprinting control. Dysregulation of 11p15 genomic imprinting results in two fetal growth disorders [Silver-Russell (SRS) and Beckwith-Wiedemann (BWS) syndromes], with opposite growth phenotypes. BWS and SRS result from abnormal imprinting involving either, both domains or only one of them, with ICR1 and ICR2 more often involved in SRS and BWS respectively. DNA methylation defects affecting ICR1 or ICR2 account for approximately 60% of SRS and BWS patients. Recent studies have identified new cis-acting regulatory elements, as well as new trans-acting factors involved in the regulation of 11p15 imprinting, therefore establishing new mechanisms of BWS and SRS. Those studies also showed that, apart of CTCF, other transcription factors, including factors of the pluripotency network, play a crucial role in the regulation of 11p15 genomic imprinting. Those new findings have direct consequences in molecular testing, risk assessment and genetic counseling of BWS and SRS patients.
© 2011 John Wiley & Sons A/S.