These findings imply that loss-of-function mutations in TSC2 might lead to the development of highly vascularized tumors, subcortical tubers, and focal atrophy of the cerebellar cortex, which are features commonly associated with TSC.
Major genes for tuberous sclerosis and autosomal dominant polycystic kidney disease, TSC2 and PKD1, respectively, lie adjacent to each other at chromosome 16p13.3, suggesting a role for PKD1 in the etiology of renal cystic disease in tuberous sclerosis.
To determine whether TSC2 RNA and protein are reduced in astrocytomas from individuals without tuberous sclerosis, reverse transcriptase-polymerase chain reaction and immunoblotting analyses were performed on 49 adult astrocytomas, 10 pediatric astrocytomas, and 13 ependymomas.
TSC exhibits locus heterogeneity: the TSC2 gene is located at 16p13.3 whilst the TSC1 gene, predicted to encode a novel protein termed hamartin, has recently been cloned from 9q34.
The presence of a deletion involving both TSC2 and PKD1 genes should be considered in the clinical assessment of TSC children with an early-onset polycystic kidney disease, and more generally in all ADPKD patients who develop end-stage renal failure prior to the fourth or fifth decade of life.
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.
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.
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.