Disease relevance of Tuberous Sclerosis

• Loss of the tumour-suppressor gene TSC1 is responsible for hamartoma development in tuberous sclerosis complex (TSC), which renders several organs susceptible to benign tumours [1].
• Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis [2].
• Images in cardiovascular medicine. Cardiac rhabdomyomas in tuberous sclerosis (Bourneville's disease) [3].
• We have recently identified the stress response REDD1 gene as a mediator of tuberous sclerosis complex (TSC)-dependent mTOR regulation by hypoxia [4].
• Individuals affected with tuberous sclerosis complex (TSC) develop several benign and malignant tumors at increased frequency, including astrocytomas [5].

Psychiatry related information on Tuberous Sclerosis

• The tuberous sclerosis complex (TSC) is a multisystem autosomal dominant disorder characterized by seizures, mental retardation, and hamartomas [6].
• Males with the tuberous sclerosis complex (TSC) have been shown to be more at risk of learning disorder than females [7].

High impact information on Tuberous Sclerosis

• gigas, a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell cycle [8].
• Tuberous sclerosis complex (TSC) is an autosomal dominant disorder of unknown aetiology that affects numerous body systems including skin, brain and kidneys [9].
• It was reported that Akt, an essential component of the insulin pathway, stimulates growth by phosphorylating and inhibiting tuberous sclerosis complex 2 (TSC2) [10].
• The tuberous sclerosis complex (TSC1-2) suppresses cell growth by negatively regulating a protein kinase, p70S6K (S6K1), which generally requires PI3K signals for its activation [11].
• The tuberous sclerosis complex gene-2 (TSC2) on chromosome 16 encodes the tumor suppressor protein tuberin [12].

Chemical compound and disease context of Tuberous Sclerosis

• A 22-year-old woman with intellectual impairment, who had been taking valproic acid continuously for 19 years since being diagnosed with epiloia at the age of 3 years, presented to our hospital following the sudden development of epigastric pain [13].
• Tc-99m HDP bone scan showing bone changes in a case of tuberous sclerosis or Bourneville's disease [14].

Biological context of Tuberous Sclerosis

• Linkage of tuberous sclerosis complex (TSC), an autosomal dominant disorder, to markers on chromosome 9 was reported first in 1987 [15].
• LAM lesions result from the proliferation of benign-appearing, smooth muscle-like LAM cells, which are characterized by loss of heterozygosity (LOH) of one of the tuberous sclerosis complex (TSC) genes [16].
• Six families with mosaicism are identified in a series of 62 unrelated families with a mutation in one of the two tuberous sclerosis complex (TSC) genes, TSC1 or TSC2 [17].
• Tuberin, the protein product of the tuberous sclerosis complex-2 (TSC2) tumor suppressor gene, has been shown to directly inhibit cell growth and is expressed at high levels in normal central nervous system neurons and astrocytes [5].
• The pathology associated with tuberous sclerosis complex (TSC) shows diverse phenotypes that suggest abnormal signaling of multiple pathways [18].

Anatomical context of Tuberous Sclerosis

• Heterozygosity for the tuberous sclerosis complex (TSC) gene products results in increased astrocyte numbers and decreased p27-Kip1 expression in TSC2+/- cells [19].
• Individuals affected with tuberous sclerosis complex (TSC) develop cortical tubers characterized by disorganized cytoarchitecture and morphologically abnormal cell types, such as dysplastic neurons (DNs) and giant cells (GCs) [20].
• Regulation of cell morphology and adhesion by the tuberous sclerosis complex (TSC1/2) gene products in human kidney epithelial cells through increased E-cadherin/beta-catenin activity [21].
• Neuropathological studies of brain lesions in tuberous sclerosis complex (TSC) have demonstrated disordered myelin sheaths [22].
• In 2 cases of tuberous sclerosis complex (TSC), a disseminated distribution of atypical cells throughout the white matter and cortex of the telencephalon has been found [23].

Gene context of Tuberous Sclerosis

• Tuberous sclerosis complex (TSC) is a genetic disease caused by mutation in either TSC1 or TSC2 [24].
• Ninety patients with tuberous-sclerosis complex (TSC) were tested for subtle mutations in the TSC2 gene, by means of single-strand conformational analysis (SSCA) of genomic DNA [25].
• Loss of tuberous sclerosis complex 1 (Tsc1) expression results in increased Rheb/S6K pathway signaling important for astrocyte cell size regulation [26].
• Recent studies reveal that the tuberous sclerosis complex (TSC)-1/2, PTEN, and LKB1 tumor suppressor proteins tightly control mTOR [27].
• Three different progression pathways were proposed: The first operative pathway is from dysplasia to superficial papillary pathologic Ta (pTa) tumors to pT1 tumors and, ultimately, to pT2 tumors with FGFR3 and tuberous sclerosis complex 1 (TSC1) the responsible genes [28].

Analytical, diagnostic and therapeutic context of Tuberous Sclerosis

• METHODS: A cross sectional questionnaire survey which included questions on 14 LAM symptoms, pneumothorax, tuberous sclerosis complex (TSC), date of diagnosis, and pulmonary function tests (PFTs) [29].
• The authors assessed whether magnetoencephalography/magnetic source imaging (MEG/MSI) identified epileptogenic zones in patients with tuberous sclerosis complex (TSC) [30].

References