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Functional characterization of the TSC2 c.3598C>T (p.R1200W) missense mutation that co‐segregates with tuberous sclerosis complex in mildly affected kindreds
Author(s) -
Wentink M,
Nellist M,
HoogeveenWesterveld M,
Zonnenberg B,
van der Kolk D,
van Essen T,
Park SM,
Woods G,
CohnHokke P,
Brussel W,
Smeets E,
Brooks A,
Halley D,
van den Ouweland A,
MaatKievit A
Publication year - 2012
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2011.01648.x
Subject(s) - tsc2 , tuberous sclerosis , tsc1 , missense mutation , phenotype , mutation , genetics , biology , gene , medicine , pathology , pi3k/akt/mtor pathway , apoptosis
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.