Samples from fetuses (n = 13 after terminations) and newborns (n = 2) were available for targeted genomic sequencing of the exons and introns of the TSC1 and TSC2 genes and the adjacent 10 base pairs and for validated studies using Sanger sequencing.Among the 15 subjects with suspected cardiac rhabdomyoma and TSC genomic sequencing data, 7 subjects were familial and 8 subjects were sporadic cases.
This Review describes important advances in the TSC field and highlights several remaining critical knowledge gaps: the factors that promote aggressive behaviour by a subset of TSC-associated RCCs; the molecular mechanisms underlying early-onset cystogenesis in TSC2-PKD1 contiguous gene deletion syndrome; the effect of early, long-term mTORC1 inhibition on the development of TSC renal disease; and the identification of the cell or cells of origin of angiomyolipomas.
After four patients with TSC and unknown mutational status (two with MFF) were excluded, MFF was detected in 53% (10 of 19) of patients with TSC1 mutation, 65% (11 of 17) of patients with TSC2 mutation, and 12% (one of eight) of patients with TSC but without an identified mutation (P = .044).
Tuberous Sclerosis Complex (TSC) is an often severe neurodevelopmental disorder caused by overactivation of the mTOR pathway due to mutations in either the TSC1 or TSC2 genes.
The prevalence of MR was 50.0% for the patients with tuberous sclerosis complex-1 (TSC1) mutation, 54.5% for TSC2 (p=0.561), 54.7% for patients with protein-truncating (PT) and 50.0% for patients with nontruncating (NT) (p=0.791), and 54.3% for patients with family history and 53.7% for patients without family history (p=0.748).
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.
We conclude that large deletions in TSC1 and TSC2 account for about 0.5 and 6% of mutations seen in TSC patients, respectively, and MLPA is a highly sensitive and accurate detection method, including for mosaicism.
Genetic loss of TSC1/TSC2 function in tuberous sclerosis complex (TSC) results in overactivation of the mammalian target of rapamycin complex 1 pathway, leading to cellular dysplasia.
In PLAM patients, with and without clinical tuberous sclerosis, mutations in the tuberous sclerosis complex involving the proteins hamartin and tuberin have been found.
Cyst-like cortical tubers are strongly associated with TSC2 gene mutation and a more aggressive seizure phenotype in patients with tuberous sclerosis complex.
In summary, we identified a novel small deletion mutation in TSC2 associated with severe TSC in a Korean family that enhances the activation of mTOR signaling in vitro.
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder caused by mutations in either of two genes, TSC1 or TSC2, resulting in the constitutive activation of the mammalian target of rapamycin complex 1 (mTORC1). mTOR inhibitors are now considered the treatment of choice for TSC disease.
This finding, coupled with the mild physical expression of TSC in some family members, supports a hypothesis that the TSC2 gene may present phenotypically as mild skin signs and significant behavioural problems.
High-throughput sequencing and multiplex ligation-dependent probe amplification (MLPA) were used to examine tuberous sclerosis complex (TSC)-related genes (TSC1 and TSC2) and their splicing regions using peripheral blood DNA from two probands in two families with TSC and to identify the genetic mutation sites.
Here, we show that TSC2-deficient cells exhibit rapid uptake of [<sup>18</sup>F]FCH <i>in vivo</i> and can be visualized by PET imaging in preclinical models of TSC/LAM, including subcutaneous tumors and pulmonary nodules.
A defect in protein farnesylation suppresses a loss of Schizosaccharomyces pombe tsc2+, a homolog of the human gene predisposing to tuberous sclerosis complex.
Inactivating TSC1 and TSC2 mutations cause tuberous sclerosis complex (TSC), an autosomal dominant disorder characterised by the occurrence of benign tumours in various organs and tissues, notably the brain, skin and kidneys.
CBD has been reported to decrease seizures and inhibit tumour cell progression, therefore we sought to determine the influence of CBD on TSC pathology in zebrafish carrying a nonsense mutation in the tsc2 gene.
Immunocytochemical analysis of the TSC brain lesions confirmed the cell-specific activation of the mTOR pathway in cortical tubers, SENs and cerebellum, as well as differential cellular localization of hamartin and tuberin, the TSC1 and TSC2 gene products.
Subtle, non-truncating mutations identified in patients with tuberous sclerosis and located within the putative binding regions of hamartin (N198_F199delinsI;593-595delACT) or tuberin (G294E and I365del), abolished or dramatically reduced interaction of the proteins as assessed by yeast two-hybrid assays and by co-immunoprecipitation of the full-length proteins from Cos7 cells.