The tuberous sclerosis (TSC) genes, TSC1 and TSC2, encode hamartin and tuberin, respectively, and are putative tumor suppressor genes that were originally identified due to their involvement in the inherited autosomal dominant disorder tuberous sclerosis.
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.
Using mouse genetics, we find that at the lowest concentrations of metformin that inhibit hepatic mTORC1 signaling, this inhibition is dependent on AMPK and the tuberous sclerosis complex (TSC) protein complex (TSC complex).
TS pathology is caused by mutations in tuberous sclerosis complex (TSC) genes and is associated with insulin resistance, decreased glycogen synthase kinase 3β (GSK3β) activity, activation of the mammalian target of rapamycin complex 1 (mTORC1), and subsequent increase in protein synthesis.
Both diseases are caused by mutations of TSC1 or TSC2 (TSC is tuberous sclerosis complex) that impair GAP (GTPase-activating protein) activity of the TSC1-TSC2 complex for Rheb, leading to inappropriate activity of signalling downstream of mTORC1 (mTOR complex 1). mTOR inhibitors are already used in a variety of clinical settings including as immunosuppressants, anticancer agents and antiproliferative agents in drug-eluting coronary artery stents.
MFF was highly specific for TSC.MFF presence was associated with TSC gene mutations and with brain or multiorgan involvement; their number per patient was correlated with the degree of multiorgan involvement.
In tuberous sclerosis complex (TSC), a substantially increased risk of developing epilepsy is present as a result of a disruption of a TSC gene expression in the brain and secondary abnormal cellular differentiation, migration, and proliferation.
Mutations in tuberous sclerosis (TSC) genes cause the genetic disorder TSC, as well as other neoplasms, including lymphangioleiomyomatosis (LAM) and angiomyolipomas (AMLs).
Analysis of the basic genetic defect in tuberous sclerosis would be greatly expedited by definitive determination of the chromosomal location of the TSC gene or genes.
Identifying functional polymorphic variants of interacting partners affecting TSC gene functions will delineate the mechanisms leading to TSC disease severity, ultimately resulting in treatment strategies.
From this analysis, mutations in TSC genes were identified in 5 samples from the AML-TSC patients (mutation detection rate=71%) and 3 samples from AML-non-TSC patients (mutation detection rate=21%).
Tuberous sclerosis complex (TSC) is an autosomal dominant tumor-suppressor gene syndrome caused by inactivating mutations in either TSC1 or TSC2, and the TSC protein complex is an essential regulator of mTOR complex 1 (mTORC1).
Taken together, our studies raise the possibility of a gene × environment interaction between heterozygous TSC gene mutations and gestational immune activation in the pathogenesis of TSC-related ASD.
Because the product of the TSC2/Tsc2 gene (tuberin) together with hamartin, the product of another TSC gene (TSC1/Tsc1), suppresses mammalian/mechanistic target of rapamycin complex 1 (mTORC1), rapalogs have been used as therapeutic drugs for TSC.
These data support the hypothesis that both the TSC genes act as tumour suppressors and that the manifestations of TSC in patients with germline TSC mutations rise from "second hit" somatic mutations inactivating the remaining normal copy of the TSC gene.
We examined mutations of both TSC genes in 6 Japanese patients with TSC-LAM and 22 patients with sporadic LAM and identified six unique and novel mutations.
Our knowledge of TSC genetics and pathophysiology has expanded dramatically in recent years: two genetic loci were discovered in the 1990s and recent elucidation of TSC's interaction with the mTOR pathway has changed how we manage the disease.
The mechanism underlying the association of autism and TSC is as yet unclear but clinical features and neuroimaging investigations suggest that an abnormal TSC gene may directly influence the development of autism rather than it being a secondary effect of seizures or MR.
In tuberous sclerosis (TSC)-associated tumors, mutations in the TSC genes lead to aberrant activation of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. mTORC1 signaling impacts many biological processes including the epithelial-mesenchymal transition (EMT), which is suggested to promote tumor progression and metastasis in various types of cancer.
Recent studies suggest that clinical similarities between BHDS and TSC may be explained by FLCN and TSC proteins functioning on a common pathway, mammalian target of rapamycin.