Grant: Operating Grant - PA: Genetics (Bridge Funding: Research Priorities)

Neurocristopathies form a group of rare genetic diseases that result from problems with neural crest cells - a specific type of stem cells that contribute diverse specialized cells in various organs. Most of these pathologies are due to gene defects, which are also influenced by non-genetic factors. Treatment options are currently very limited, mainly consisting of invasive and non-curative surgeries. Using mouse models and cells from affected children, our main goals are to identify the molecular mechanisms shared by different neurocristopathies and use this knowledge for developing more efficient gene defect-independent therapies. The current project focusses on CHARGE syndrome - a life-threatening neurocristopathy with complex clinical presentation. Based on our recent work, we now know that multiple genes are associated with this condition. The proposed work aims to precisely understand the function of a new gene (FAM172A) and its relationship with other CHARGE syndrome-associated genes. Our preliminary data suggest that all corresponding proteins play key roles in regulating proper expression and processing of other genes. Other data suggest that correction of a least one of the affected processes might have therapeutic value. To elucidate these roles, we will use a wide array of complementary approaches in molecular and cellular biology. This work should lead to improved healthcare for children with CHARGE syndrome or other neurocristopathies.