Biochemical Characterisation of TSC1 and TSC2 Variants Identifiedd in Patients with Tuberous sclerosis Complex
Annual rept. 1 Jul 2007-30 Jun 2008
ERASMUS MEDICAL CENTER ROTTERDAM (NETHERLANDS)
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The key findings of the project during the research period are as follows 1. Derivation of 62 unclassified TSC2 variants 27 classified as pathogenic 10 classified as neutral 27 still unclassifiedanalysis not complete. 2. Derivation of 20 unclassified TSC1 variants 8 classified as pathogenic 7 classified as neutral 5 still unclassifiedanalysis not complete 3. Demonstration that TSC1 missense mutations cause TSC. 4. Identification of a region of TSC1 amino acids 50 - 224 required for maintaining TSC1 at sufficient levels in the cell to form a stable TSC1-TSC2 complex and inhibit mTOR. 5. Identification of amino acid residues involved in i TSC1-TSC2 binding, and ii rhebGAP activity. 6. Robust assay for detection of pathogenic TSC2 variants. 7. Improvements in assay cost, throughput and reproducibility.
- Genetic Engineering and Molecular Biology