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RESEARCH PRODUCT
Functional Assessment of Variants in the TSC1 and TSC2 Genes Identified in Individuals with Tuberous Sclerosis Complex
Rosemary EkongSue PoveyJoann BergoffenStephanie E. ValleeJacinta DzarirKay MetcalfeMarjolein WentinkMark NellistVandana ShashiStefan KruegerKira A. DiesConcha VidalesMarianne Hoogeveen-westerveldAns M.w. Van Den OuwelandMelika MozaffariFrances ElmslieAnneke Maat-kievitJulian R. SampsonDiana Van Den HeuvelDicky J. J. HalleyDavid J. KwiatkowskiJavier García-planellsJohan T. Den Dunnensubject
congenital hereditary and neonatal diseases and abnormalitiesGenetic counselingtuberous sclerosis complexBiologyTuberous Sclerosis Complex 1 Protein03 medical and health sciencesTuberous sclerosis0302 clinical medicineTuberous SclerosisGenetic variationTuberous Sclerosis Complex 2 ProteinGeneticsmedicineMissense mutationHumansunclassified variantsGeneGenetics (clinical)Cells Cultured030304 developmental biologyGenetics0303 health sciencesModels GeneticTumor Suppressor ProteinsLife SciencesGenetic Variationmedicine.diseaseTSC23. Good healthnervous system diseasesTSC1medicine.anatomical_structureTSC1TSC2030217 neurology & neurosurgeryCommon disease-common variantdescription
The effects of missense changes and small in-frame deletions and insertions on protein function are not easy to predict, and the identification of such variants in individuals at risk of a genetic disease can complicate genetic counselling. One option is to perform functional tests to assess whether the variants affect protein function. We have used this strategy to characterize variants identified in the TSC1 and TSC2 genes in individuals with, or suspected of having, Tuberous Sclerosis Complex (TSC). Here we present an overview of our functional studies on 45 TSC1 and 107 TSC2 variants. Using a standardized protocol we classified 16 TSC1 variants and 70 TSC2 variants as pathogenic. In addition we identified eight putative splice site mutations (five TSC1 and three TSC2). The remaining 24 TSC1 and 34 TSC2 variants were classified as probably neutral. Hum Mutat 32: 424-435, 2011. (C) 2011 Wiley-Liss, Inc.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2011-04-30 |