{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:27:04Z","timestamp":1773271624316,"version":"3.50.1"},"reference-count":44,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,11,1]]},"abstract":"<jats:sec>\n                  <jats:title>Context:<\/jats:title>\n                  <jats:p>Thyroid hormones (TH) are important for normal brain development and abnormal TH regulation in the brain results in neurocognitive impairments. The type 2 deiodinase (D2) is important for local TH control in the brain by generating the active hormone T3 from its precursor T4. Dysfunction of D2 likely results in a neurocognitive phenotype. No mutations in D2 have been reported yet.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective:<\/jats:title>\n                  <jats:p>The objective of the study was to identify D2 mutations in patients with intellectual disability and to test their functional consequences.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design, Setting, and Patients:<\/jats:title>\n                  <jats:p>The patients were selected from the multicenter Thyroid Origin of Psychomotor Retardation study, which is a cohort of 946 subjects with unexplained intellectual disability. Based on characteristic serum TH values, the coding region of the DIO2 gene was sequenced in 387 patients. Functional consequences were assessed by in vitro D2 assays or intact cell metabolism studies using cells transfected with wild-type or mutant D2.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>Sequence analysis revealed two heterozygous mutations: c.11T&amp;gt;A (p.L4H) in three subjects and c.305C&amp;gt;T (p.T102I) in one subject. Sequence analysis of family members revealed several carriers, but no segregation was observed with thyroid parameters or neurocognitive phenotype. Extensive tests with different in vitro D2 assays did not show differences between wild-type and mutant D2.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion:<\/jats:title>\n                  <jats:p>This study describes the identification and functional consequences of novel genetic variation in TH activating enzyme D2. Family studies and functional tests suggest that these variants do not underlie the neurocognitive impairment. Altogether our data provide evidence of the existence of rare but apparently harmless genetic variants of D2.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2014-2281","type":"journal-article","created":{"date-parts":[[2014,8,20]],"date-time":"2014-08-20T16:55:42Z","timestamp":1408553742000},"page":"E2429-E2436","source":"Crossref","is-referenced-by-count":6,"title":["Functional Analysis of Novel Genetic Variation in the Thyroid Hormone Activating Type 2 Deiodinase"],"prefix":"10.1210","volume":"99","author":[{"given":"Chantal","family":"Zevenbergen","sequence":"first","affiliation":[{"name":"Department of Internal Medicine (C.Z., W.K., R.P.P., M.M., Y.B.d.R., M.E.M., T.J.V., W.E.V.), Wytemaweg 80, 3015 CN Rotterdam, The Netherlands"},{"name":"Rotterdam Thyroid Center (C.Z., W.K., R.P.P., M.M., M.E.M., T.J.V., W.E.V.), Wytemaweg 80, 3015 CN Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wim","family":"Klootwijk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (C.Z., W.K., R.P.P., M.M., Y.B.d.R., M.E.M., T.J.V., W.E.V.), Wytemaweg 80, 3015 CN Rotterdam, The Netherlands"},{"name":"Rotterdam Thyroid Center (C.Z., W.K., R.P.P., M.M., M.E.M., T.J.V., W.E.V.), Wytemaweg 80, 3015 CN Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin P.","family":"Peeters","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (C.Z., W.K., R.P.P., M.M., Y.B.d.R., M.E.M., T.J.V., W.E.V.), Wytemaweg 80, 3015 CN Rotterdam, The Netherlands"},{"name":"Rotterdam Thyroid Center (C.Z., W.K., R.P.P., M.M., M.E.M., T.J.V., W.E.V.), Wytemaweg 80, 3015 CN Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Medici","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (C.Z., W.K., R.P.P., M.M., Y.B.d.R., M.E.M., T.J.V., W.E.V.), Wytemaweg 80, 3015 CN Rotterdam, The Netherlands"},{"name":"Rotterdam Thyroid Center (C.Z., W.K., R.P.P., M.M., M.E.M., T.J.V., W.E.V.), Wytemaweg 80, 3015 CN Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yolanda B.","family":"de Rijke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (C.Z., W.K., R.P.P., M.M., Y.B.d.R., M.E.M., T.J.V., W.E.V.), Wytemaweg 80, 3015 CN Rotterdam, The Netherlands"},{"name":"Department of Clinical Chemistry (Y.B.d.R.), Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvia A.","family":"Huisman","sequence":"additional","affiliation":[{"name":"Prinsenstichting (S.A.H.), Kwadijkerpark 8, 1444 JE Purmerend, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henk","family":"Goeman","sequence":"additional","affiliation":[{"name":"Ipse De Bruggen (H.G., E.B.), Spoorlaan 19, 2471 PB Zwammerdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"Boot","sequence":"additional","affiliation":[{"name":"Ipse De Bruggen (H.G., E.B.), Spoorlaan 19, 2471 PB Zwammerdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerda","family":"de Kuijper","sequence":"additional","affiliation":[{"name":"Vanboeijenoord (G.d.K.), Industrieweg 14\u201316, 9400 RA Assen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. Herman","family":"de Waal","sequence":"additional","affiliation":[{"name":"'s Heeren Loo Groot Schuilenburg (K.H.d.W.), Laan Van Groot Schuylenburg 310\u2013320, 7325 BG Apeldoorn, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel E.","family":"Meima","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (C.Z., W.K., R.P.P., M.M., Y.B.d.R., M.E.M., T.J.V., W.E.V.), Wytemaweg 80, 3015 CN Rotterdam, The Netherlands"},{"name":"Rotterdam Thyroid Center (C.Z., W.K., R.P.P., M.M., M.E.M., T.J.V., W.E.V.), Wytemaweg 80, 3015 CN Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. 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