ANALYSIS OF THE BECKWITH-WIEDEMANN SYNDROME REGION IN MOUSE MODELS AND PATIENTS

The Beckwith-Wiedemann Syndrome (BWS) is a disease characterised by somatic overgrowth, macroglossia, visceromegaly, abdominal wall defects and increased risk of developing pediatric cancer. BWS is genetically heterogeneous and shows extremely variable clinical phenotype. The molecular data available suggest that BWS and possibly other related overgrowth disorders are caused by deregulation of genes located on chromosome 11p15.5 and characterised by genomic imprinting. This 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. The most frequent molecular abnormalities in BWS are indeed DNA methylation defects. However, their identification is still incomplete and the molecular pathogenesis of BWS is undefined. In this project, we propose to use animal models to define the regulatory mechanisms of the BWS genes and use these informations to identify the molecular defects and give insights into the pathogenesis of this disease.