Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting 1 in 6,000 births, that is characterized by benign tumors (hamartomas and hamartias) in multiple organ systems. Its major clinical manifestations are due to brain involvement -- seizures, mental retardation and autism and related disorders, each of which occur in about half of TSC patients. The existence of two genes (TSC1 and TSC2) causing this disorder was established by familiar genetic linkage studies. TSC2 was identified 4 years ago, and has weak GTPase activating protein (GAP) activity for two members of the Ras family of GTPases, rap1 and rab5. In the previous application, the PI proposed to identify the TSC1 gene by positional cloning. This is now accomplished by a collaborative effort by several laboratories. There are three specific aims in the competitive renewal application: 1) A detailed mutational analysis will be performed for both the TSC1 and TSC2 loci; 2) Development of murine models of TSC; and 3)Analysis of the function of TSC1 and TSC2 proteins, hamartin and tuberin.
Showing the most recent 10 out of 46 publications