{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:35:30Z","timestamp":1782452130915,"version":"3.54.5"},"reference-count":19,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,3,10]],"date-time":"2011-03-10T00:00:00Z","timestamp":1299715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:p>Wentink M, Nellist M, Hoogeveen\u2010Westerveld M, Zonnenberg B, van der Kolk D, van Essen T, Park S\u2010M, Woods G, Cohn\u2010Hokke P, Brussel W, Smeets E, Brooks A, Halley D, van den Ouweland A, Maat\u2010Kievit A. Functional characterization of the <jats:italic>TSC2<\/jats:italic> c.3598C&gt;T (p.R1200W) missense mutation that co\u2010segregates with tuberous sclerosis complex in mildly affected kindreds.<\/jats:p><jats:p>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 <jats:italic>TSC1<\/jats:italic> and <jats:italic>TSC2<\/jats:italic> genes. Overall, <jats:italic>TSC2<\/jats:italic> mutations are associated with a more severe disease phenotype. We identified the c.3598C&gt;T (R1200W) change in the <jats:italic>TSC2<\/jats:italic> 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\u2013TSC2 function. Interestingly however, in each case, the TSC1\u2013TSC2 interaction was not affected by the amino acid substitution.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2011.01648.x","type":"journal-article","created":{"date-parts":[[2011,2,17]],"date-time":"2011-02-17T14:51:23Z","timestamp":1297954283000},"page":"453-461","source":"Crossref","is-referenced-by-count":35,"title":["Functional characterization of the <i>TSC2<\/i> c.3598C&gt;T (p.R1200W) missense mutation that co\u2010segregates with tuberous sclerosis complex in mildly affected 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