Epigenetic and Genetic Mechanisms of Abnormal 11p15 Genomic Imprinting in Silver-Russell and Beckwith-Wiedemann Syndromes

J.      Demars; Y.      Le Bouc; A.      El-Osta; C.      Gicquel

Abstract

Fetal growth is a complex process depending on the genetics of the fetus, the availability of nutrients to the fetus, maternal nutrition and various growth factors and hormones of maternal, fetal and placental origin. The IGF system, and more particularly IGF2, is one of the most important endocrine and paracrine growth systems regulating fetal and placental growth (reviewed in [1]). The IGF2 gene is regulated by genomic imprinting and is expressed only from the paternally-inherited allele in most tissues during fetal development and after birth.

Imprinted genes are tightly regulated and are therefore particularly susceptible to changes, including environmental and nutritional changes. Dysregulation of a cluster of imprinted genes, including the IGF2 gene within the 11p15 region, results in two fetal growth disorders (Silver-Russell and Beckwith-Wiedemann syndromes) with opposite growth phenotypes. Those two syndromes are model imprinting disorders to decipher the regulation of genomic imprinting.

Keywords: Genomic imprinting, 11p15 region, fetal growth, Silver-Russell syndrome, Beckwith-Wiedemann syndrome, imprinting cycle, cis-regulatory element, trans-acting regulatory factor, genetics, DNA