Functional characterization of the TSC2 c.3598C > T (p.R1200W) missense mutation that co-segregates with tuberous sclerosis complex in mildly affected kindreds

M. Wentink, M. Nellist, M. Hoogeveen-Westerveld, B. Zonnenberg, Dorina M. van der Kolk, Ton van Essen, S-M Park, C. Geoffrey Woods, Petra E. Cohn-Hokke, W. Brussel, E. Smeets, Anthony Brooks, Dicky J. J. Halley, Ans M. W. van den Ouweland, J. A. Maat-Kievit*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

22 Citations (Web of Science)


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.
Original languageEnglish
Pages (from-to)453-461
JournalClinical Genetics
Issue number5
Publication statusPublished - May 2012


  • mild phenotype
  • missense mutation
  • TSC2
  • tuberous sclerosis complex

Cite this