Molecular mechanisms underlying Joubert syndrome

Joubert syndrome (JS) is a rare genetic disease in infants and children which is characterized by cerebellum defects, a variety of neurologic symptoms as well as abnormalities in skeleton, kidneys and retina. About 30 genes have been found responsible for this syndrome. Recently, it has been found that alteration of one gene known as PDE6δ causes a subtype of Joubert syndrome, called Joubert syndrome-22 (JBTS22). Our lab has recently demonstrated that the PDE6δ protein is associated with a protein called FBXL2 which is responsible for the destruction of a number of proteins localized at cellular membranes. We have also found that the PDE6δ alteration present in individuals with Joubert syndrome blocks the association of PDE6δ with FBXL2. The overall objective of this project is to study the molecular mechanisms underlying Joubert syndrome-22 (JBTS22) focusing particularly on protein destruction. These findings will be important for identifying new potential drugs for this disease.