The genetics and function of tuberin and hamartin in the pathogenesis of tuberous sclerosis complex (TS) are reviewed in a presentation at a “Festschrift” honoring Dr Michael J Painter of the Division of Pediatric Neurology, Children’s Hospital of Pittsburgh, PA. The prevalence of TS is 1/10,000, two-thirds being sporadic. Among familial cases, half are linked to chromosome 9q34 (TSC1) locus and half to the 16pl3.3 (TSC2) locus. Most sporadic cases are due to defects in TSC2. The TSC1 gene encodes the protein, hamartin, and the TSC2 gene encodes tuberin. The gene for polycystic kidney disease is located centromeric to TSC2, accounting for the occurrence of both conditions in families with contiguous gene syndromes. Tuberin and hamartin function as tumor suppressors, inhibiting the activity of rapamycin (mTOR) and regulating cell growth. [1]

COMMENT. It is suggested that knowledge of the cellular functions of tuberin and hamartin might lead to new drugs that modulate signaling pathways. These could be effective in the control of epilepsy and cognitive impairment associated with TS. The discovery of tumor suppressor genes has provided insight into genetic alterations that contribute to neoplasia. These genes contribute to tumorigenesis only when both alleles have been inactivated. [2]