The recently reported loss of heterozygosity (LOH) at the regions of the TSC1 or TSC2 locus in hamartomas obtained from different organs of patients with established tuberous sclerosis, including cortical tubers, stimulated us to examine epilepsy-associated tuberous sclerosis-like glioneuronal malformations with respect to LOH at the TSC1 and TSC2 loci of chromosomes 9q34 and 16p 13.3, respectively.
Tuberin has been immunolocalized to neurons and possibly astrocytes in normal brain and CD/TSC tubers, and is widely expressed in normal viscera; loss of heterozygosity and tissue culture studies suggest it functions as a growth suppressor.
Diagnostic testing will be difficult because of the genetic heterogeneity of TSC (which has at least two causative genes: TSC1 and TSC2), the large size of the TSC2 gene, and the variety of mutations.
Our laboratory has undertaken the complete mutation analysis of the TSC2 gene in 42 TSC families using single-strand conformation polymorphism analysis and reverse transcription-polymerase chain reaction.
We discuss and illustrate neuropathologic features of both CD and TSC, and discuss the patterns and time course of hamartin/tuberin expression in normal brain, CD and TSC.
Mutation analyses in tuberous sclerosis (TSC) have reported a wide variety of disease-causing aberrations in the two known predisposing genes, TSC1 and TSC2 on chromosomes 9q34 and 16p13, comprising mainly small mutations distributed over the entire genes.
Our results suggest that tuberin and hamartin are both robustly expressed in similar populations of neuroglial cells of TSC tubers, even in the presence of TSC1 or TSC2 germline mutations.
Tuberous sclerosis (TSC) is a dominantly inherited disorder due to mutations at two gene loci, the TSC1 locus on chromosome 9q34 and the TSC2 locus on chromosome 16p13.3.
We recently found that 54% of these angiomyolipomas have TSC2 loss of heterozygosity, leading to the hypothesis that sporadic LAM is genetically related to TSC.
The cell-specific expression of tuberin and hamartin described here will provide critical insight into the cell types that give rise to kidney lesions, and the tumor suppressor role of these proteins in TSC.