Biochemical Characterisation of TSC1 and TSC2 Variants Identifiedd in Patients with Tuberous sclerosis Complex
Abstract
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 unclassified/analysis not complete. 2. Derivation of 20 unclassified TSC1 variants: 8 classified as pathogenic; 7 classified as neutral; 5 still unclassified/analysis 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2008
- Accession Number
- ADA622174
Entities
People
- Dicky Halley
- Marianne Hoogeveen-westerveld
- Mark Nellist
Organizations
- Erasmus MC