Inactivating germline mutations of TSC2 in patients with tuberous sclerosis and somatic loss of heterozygosity at the TSC2 locus in the associated hamartomas indicate that TSC2 functions as a tumour suppressor gene and that loss of function is critical to expression of the tuberous sclerosis phenotype.
The gene products hamartin and tuberin form the TSC complex that acts as GTPase-activating protein for Rheb and negatively regulates the mammalian target of rapamycin complex 1 (mTORC1).
We have analyzed the distribution of TSC2 mRNA and tuberin in the brains of TSC patients and non-affected individuals using both autopsy and biopsy material.
Acrochordons are a common skin lesion, but when presenting in an atypical manner or unusual number may be a sign of TSC and underlying occult pathology thereby warranting evaluation of TSC2.
Functional characterisation of TSC2 variants can help identify pathogenic changes in individuals with TSC, and assist in the diagnosis and genetic counselling of the index cases and/or other family members.
Here, we report one novel mutation of TSC1 (Q897X) and five novel mutations of TSC2 (c.336+1 G>A, L345R, E700K, R905G, K914K) identified in Japanese patients with TSC.
All the exons of TSC1 and TSC2 were analyzed by using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) in DNA separated from peripheral blood of 28 patients with TSC and 100 normal controls.
We have previously shown that denaturing high-performance liquid chromatography (DHPLC) at the recommended melt temperature can detect TSC1 and TSC2 mutations in tuberous sclerosis patients with low-level somatic mosaicism, even when direct sequencing cannot identify the causative lesion.
During conditions of cell stress, GADD34 forms a stable complex with tuberous sclerosis complex (TSC) 1/2, causes TSC2 dephosphorylation, and inhibits signaling by mammalian target of the rapamycin (mTOR).
The tuberous sclerosis tumor suppressors TSC1 and TSC2 form a protein complex that integrates and transmits cellular growth factor and stress signals to negatively regulate TOR activity.