Functional role of Ezh2 mutations in Weaver Syndrome

Weaver syndrome is a very rare disease, which takes its name from the researcher who first described it in 1974, David Weaver. Patients who suffer from this syndrome show abnormal growth due to excessive bone development associated with a number of craniofacial abnormalities, neurological and limb defects. The majority of patients also suffer from mental retardation. Despite the gravity of the deformations carried by patients with Weaver syndrome, the disease does not appear to adversely affect life expectancy, which is statistically identical to that of the healthy population. In 2011, Ezh2 was identified as the gene affected in Weaver patients. The protein Ezh2 regulates developmental processes and it’s involved in the modulation of osteogenesis, myogenesis, lymphogenesis and hematopoiesis, as well as tumor cells growth. The aim of our project is to study how the abnormal function of Ezh2 leads to improper regulation of genes important for development and growth. We will use normal Ezh2 and the defective Ezh2 found in Weaver patients to study why the Ezh2-Weaver form works less efficiently than the normal Ezh2. We will use an in vitro approach and we will employ cultured cell lines. Our work will provide insights into the molecular mechanisms underlying Weaver Syndrome.