Major genes which cause tuberous sclerosis (TSC) and autosomal dominant polycystic kidney disease (ADPKD), known as TSC2 and PKD1 respectively, lie immediately adjacent to each other on chromosome 16p.
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.
However, a number of patients with large deletions of the PKD1 and adjacent tuberous sclerosis 2 (TSC2) genes, who have tuberous sclerosis and severe childhood-onset polycystic kidney disease, have also been described.
Tuberous sclerosis complex is an autosomal dominant disorder with loci on chromosome 9q34 (TSC1) and chromosome 16p13.3 (TSC2).The TSC2 gene has been isolated.
The identification of the TSC1 gene on chromosome 9q, along with functional studies and mutational analyses of both TSC genes, will likely provide fascinating insights into the pathogenesis of TSC.
Tuberous sclerosis complex is an autosomal dominant disorder with loci on chromosome 9q34 (TSC1) and chromosome 16p13.3 (TSC2).The TSC2 gene has been isolated.
The identification of the TSC1 gene on chromosome 9q, along with functional studies and mutational analyses of both TSC genes, will likely provide fascinating insights into the pathogenesis of TSC.
The identification of the TSC1 gene on chromosome 9q, along with functional studies and mutational analyses of both TSC genes, will likely provide fascinating insights into the pathogenesis of TSC.
However, a number of patients with large deletions of the PKD1 and adjacent tuberous sclerosis 2 (TSC2) genes, who have tuberous sclerosis and severe childhood-onset polycystic kidney disease, have also been described.
Allelic loss or loss of heterozygosity (LOH) in TSC lesions has previously been reported on chromosomes 16p13 and 9q34, the locations of the TSC2 and TSC1 genes, respectively, suggesting that the TSC genes act as tumor-suppressor genes.
To investigate the molecular mechanisms of tuberous sclerosis (TSC) histopathologic lesions, we have tested for loss of heterozygosity the two TSC loci (TSC1 and TSC2) and seven tumor suppressor gene-containing regions (TP53, NF1, NF2, BRCA1, APC, VHL, and MLM) in 20 hamartomas from 18 TSC patients.
We have previously described in tuberous sclerosis (TSC) hamartomas the phenomenon of loss of heterozygosity (LOH) for DNA markers in the region of both the TSC2 gene on chromosome 16p13.3 and the TSC1 gene on 9q34.
Visceral TSC2 expression was comparable in autopsy tissues from patients with and without TSC; TSC2 messenger RNA expression was most prominent in cells with a rapid mitotic rate and turnover, e.g., epithelia and lymphocytes, with central nervous system pyramidal cells and other neurons being an obvious exception, and/or in cells with important secretory/transport functions.