The molecular genetics of tuberous sclerosis

Julian R. Sampson, Peter C. Harris

Research output: Contribution to journalShort surveypeer-review

93 Scopus citations


Tuberous sclerosis (TSC) is an autosomal dominant trait characterized by the widespread development of benign tumours classified as hamartoma, and is often associated with seizures and mental retardation. The patchy distribution and focal nature of the growths suggests that they might result from inactivation of a tumour suppressor gene by a two-hit process. Over the last 2 years, studies designed to investigate both germline and somatic TSC mutations have lent support to this hypothesis. Analysis of TSC-associated hamartomas has shown loss of heterozygosity for the regions of chromosomes 9 and 16 known to harbour TSC genes, consistent with the occurrence of somatic 'second-hit' mutations. Parallel investigations using pulse field gel electrophoresis have identified constitutional deletions representing 'first-hit' mutations at 16p13.3, leading to the rapid identification of one of the causative genes, TSC2. Intriguingly, the TSC2 product, tuberin, has an area of sequence homology with the GTPase activating protein rap1 GAP, suggesting a possible mechanism for its role in regulating cellular growth.

Original languageEnglish (US)
Pages (from-to)1477-1480
Number of pages4
JournalHuman molecular genetics
Issue numberREVIEW
StatePublished - 1994

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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