Molecular bases of the Beckwith-Wiedemann Syndrome and Silver-Russell Syndrome

The Beckwith-Wiedemann Syndrome (BWS) is a disease characterized by somatic overgrowth, macroglossia, visceromegaly, abdominal wall defects and increased risk of developing pediatric cancer. The Silver-Russell syndrome (SRS) is characterized by severe intra-uterine and postnatal growth retardation and typical dysmorphic features. Both BWS and SRS are caused by dysregulation of imprinted genes. Genomic imprinting is a mechanism causing the expression of a gene to depend on its origin from mother or father. This process is controlled by epigenetic modifications, that are heritable characteristics of a gene (such as DNA methylation) not coded by its nucleotide sequence. Epigenetic defects and altered expression of imprinted genes of opposite types have been involved in BWS and SRS and are more frequently found among children conceived after use of Assisted Reproduction Technology. The aim of this research project is to define the molecular bases of BWS and SRS, in order to improve molecular diagnosis, patients stratification and management, and to identify new therapeutic targets.