Functional characterization of the TSC2 c.3598C>T (p.R1200W) missense mutation that co-segregates with tuberous sclerosis complex in mildly affected kindreds
Version of Record online: 10 MAR 2011
© 2011 John Wiley & Sons A/S
Volume 81, Issue 5, pages 453–461, May 2012
How to Cite
Wentink, M., Nellist, M., Hoogeveen-Westerveld, M., Zonnenberg, B., van der Kolk, D., van Essen, T., Park, S.-M., Woods, G., Cohn-Hokke, P., Brussel, W., Smeets, E., Brooks, A., Halley, D., van den Ouweland, A. and Maat-Kievit, A. (2012), Functional characterization of the TSC2 c.3598C>T (p.R1200W) missense mutation that co-segregates with tuberous sclerosis complex in mildly affected kindreds. Clinical Genetics, 81: 453–461. doi: 10.1111/j.1399-0004.2011.01648.x
- Issue online: 11 APR 2012
- Version of Record online: 10 MAR 2011
- Accepted manuscript online: 17 FEB 2011 08:28AM EST
- Received 13 December 2010, revised and accepted for publication 14 February 2011
- mild phenotype;
- missense mutation;
- tuberous sclerosis complex
Wentink M, Nellist M, Hoogeveen-Westerveld M, Zonnenberg B, van der Kolk D, van Essen T, Park S-M, Woods G, Cohn-Hokke P, Brussel W, Smeets E, Brooks A, Halley D, van den Ouweland A, Maat-Kievit A. Functional characterization of the TSC2 c.3598C>T (p.R1200W) missense mutation that co-segregates with tuberous sclerosis complex in mildly affected kindreds.
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by a combination of neurological symptoms and hamartomatous growths, and caused by mutations in the TSC1 and TSC2 genes. Overall, TSC2 mutations are associated with a more severe disease phenotype. We identified the c.3598C>T (R1200W) change in the TSC2 gene in seven different families. The clinical phenotypes in the families were mild, characterized by mild skin lesions, remitting epilepsy and a lack of severe mental retardation or major organ involvement. Functional analysis of the TSC2 R1200W variant, and four other TSC2 missense variants associated with a mild TSC phenotype, confirmed that the changes disrupted the TSC1–TSC2 function. Interestingly however, in each case, the TSC1–TSC2 interaction was not affected by the amino acid substitution.