1043-3155 Pediatr Neurol Briefs pedneurbriefs Pediatr Neurol Briefs Pediatric Neurology Briefs Pediatr Neurol Briefs 2166-6482 1043-3155 2166-3155 Pediatric Neurology Briefs Publishers Chicago, IL, USA PNB-18-06 10.15844/pedneurbriefs-18-1-7 Neurocutaneous Syndromes Neurology Pediatrics Nervous System Diseases Child Development Brain Diseases Neurosurgery Child Infant Function of Tuberin and Hamartin in Tuberous Sclerosis Pathogenesis http://orcid.org/0000-0002-0173-7931 Millichap J. Gordon MD 1 2 * Division of Neurology, Children's Memorial Hospital, Chicago, IL Departments of Pediatrics and Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL Correspondence: Dr. J. Gordon Millichap, E-mail: jgmillichap@northwestern.edu 01 2004 01 03 2016 18 1 6 6 Copyright: © 2004 The Author(s) 2004 This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Tuberous sclerosis complex: genetics to pathogenesis

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.

 Tuberin and Hamartin Tuberous Sclerosis Complex Festschrift

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]

Narayanan V Tuberous sclerosis complex: genetics to pathogenesis Pediatr Neurol 2003 Nov 29 5 404 409 10.1016/j.pediatrneurol.2003.09.002 14684235 Charrow J Progress in Pediatric Neurology III 1997 PNB Publ 435 439 Chpt 10