TY - JOUR
T1 - Functional characterization of the TSC2 c.3598C > T (p.R1200W) missense mutation that co-segregates with tuberous sclerosis complex in mildly affected kindreds
AU - Wentink, M.
AU - Nellist, M.
AU - Hoogeveen-Westerveld, M.
AU - Zonnenberg, B.
AU - van der Kolk, Dorina M.
AU - van Essen, Ton
AU - Park, S-M
AU - Woods, C. Geoffrey
AU - Cohn-Hokke, Petra E.
AU - Brussel, W.
AU - Smeets, E.
AU - Brooks, Anthony
AU - Halley, Dicky J. J.
AU - van den Ouweland, Ans M. W.
AU - Maat-Kievit, J. A.
PY - 2012/5
Y1 - 2012/5
N2 - 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.
AB - 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.
KW - mild phenotype
KW - missense mutation
KW - TSC2
KW - tuberous sclerosis complex
U2 - 10.1111/j.1399-0004.2011.01648.x
DO - 10.1111/j.1399-0004.2011.01648.x
M3 - Article
C2 - 21332470
SN - 0009-9163
VL - 81
SP - 453
EP - 461
JO - Clinical Genetics
JF - Clinical Genetics
IS - 5
ER -