Article: Genes and Disease: Tuberous sclerosis

Tuberous sclerosis

Tuberous sclerosis is an hereditary disorder characterized by benign, tumor-like nodules of the brain and/or retinas, skin lesions, seizures and/or mental retardation. Patients may experience a few or all of the symptoms with varying degrees of severity.

Two loci for tuberous sclerosis have been found: TSC1 on chromosome 9, and TSC2 on chromosome 16. It took four years to pin down a specific gene from the TSC1 region of chromosome 9: in 1997, a promising candidate was found. Called hamartin by the discoverers, it is similar to a yeast protein of unknown function, and appears to act as a tumor suppressor: without TSC1, growth of cells proceeds in an unregulated fashion, resulting in tumor formation. TSC2 codes for a protein called tuberin, which, through database searches, was found to have a region of homology to a protein found in pathways that regulate the cell (GAP3, a GTPase-activation protein).

SC1 has a homolog in yeast, which provides a system in which to model the human disease.