{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:25:17Z","timestamp":1783488317700,"version":"3.55.0"},"reference-count":26,"publisher":"The Endocrine Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,5,1]]},"abstract":"<jats:p>Context: Resistance to thyroid hormone (RTH) is a dominantly inherited syndrome of variable tissue hyporesponsiveness to thyroid hormone (TH).<\/jats:p>\n                  <jats:p>Objective: We report a newborn who presented with severe RTH (Mkar) with serum TSH 1500 mU\/liter and free T3 greater than 50 pm (normal 3.1\u20139.4) and free T4 25.3 pm (normal 12\u201322). We hypothesized that the RTH was due to reduced ligand binding and\/or abnormal interaction with nuclear cofactors.<\/jats:p>\n                  <jats:p>Design: These were prospective in vivo and in vitro studies.<\/jats:p>\n                  <jats:p>Setting: The study was conducted at a tertiary care university hospital.<\/jats:p>\n                  <jats:p>Patients: Patients included a newborn child and two other subjects with RTH.<\/jats:p>\n                  <jats:p>Intervention: The effect of various TH-lowering agents in the subject with RTH was studied. In vitro studies including EMSA and mammalian two-hybrid assay as well as in vitro transfection studies were conducted.<\/jats:p>\n                  <jats:p>Main Outcome Measures: Sequencing of the TH receptor (TR)\u03b2 and in vitro measurements of receptor-cofactor interaction were measured.<\/jats:p>\n                  <jats:p>Results: Sequencing of the TR\u03b2 demonstrated a de novo heterozygous mutation, 1590_1591insT, resulting in a frameshift producing a mutant TR\u03b2 (mutTR)-\u03b2 with a 28-amino acid (aa) nonsense sequence and 2-amino acid carboxyl-terminal extension. The Mkar mutation was evaluated in comparison to three other TR\u03b2 frameshift mutations in the carboxyl terminus. EMSA demonstrated that the Mkar mutTR\u03b21 had impaired ability to recruit nuclear receptor corepressor but intact association with silencing mediator of retinoid and thyroid receptor (SMRT).<\/jats:p>\n                  <jats:p>Conclusion: Our data suggest that alterations in codons 436\u2013453 in helix 11 result in significantly diminished association with nuclear receptor corepressor but not SMRT. This novel mutTR\u03b2 demonstrates nuclear corepressor specificity that results in severe predominantly pituitary RTH due to impaired release of SMRT.<\/jats:p>","DOI":"10.1210\/jc.2005-2428","type":"journal-article","created":{"date-parts":[[2006,2,7]],"date-time":"2006-02-07T21:59:26Z","timestamp":1139349566000},"page":"1887-1895","source":"Crossref","is-referenced-by-count":37,"title":["A Novel Thyroid Hormone Receptor-\u03b2 Mutation That Fails to Bind Nuclear Receptor Corepressor in a Patient as an Apparent Cause of Severe, Predominantly Pituitary Resistance to Thyroid Hormone"],"prefix":"10.1210","volume":"91","author":[{"given":"Sharon Y.","family":"Wu","sequence":"first","affiliation":[{"name":"Departments of Medicine (S.Y.W., R.N.C., H.G., J.N., S.R., R.E.W.), Chicago Illinois 60645"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald N.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Departments of Medicine (S.Y.W., R.N.C., H.G., J.N., S.R., R.E.W.), Chicago Illinois 60645"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enver","family":"Simsek","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (E.S., D.A.S., N.E.Y.), Abant Izzet Baysal University, Duzce Medical School, 14450 Duzce, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dursun A.","family":"Senses","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (E.S., D.A.S., N.E.Y.), Abant Izzet Baysal University, Duzce Medical School, 14450 Duzce, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nese E.","family":"Yar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (E.S., D.A.S., N.E.Y.), Abant Izzet Baysal University, Duzce Medical School, 14450 Duzce, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Grasberger","sequence":"additional","affiliation":[{"name":"Departments of Medicine (S.Y.W., R.N.C., H.G., J.N., S.R., R.E.W.), Chicago Illinois 60645"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Noel","sequence":"additional","affiliation":[{"name":"Departments of Medicine (S.Y.W., R.N.C., H.G., J.N., S.R., R.E.W.), Chicago Illinois 60645"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Refetoff","sequence":"additional","affiliation":[{"name":"Departments of Medicine (S.Y.W., R.N.C., H.G., J.N., S.R., R.E.W.), Chicago Illinois 60645"},{"name":"Pediatrics (S.R.), University of Chicago, Chicago Illinois 60645"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy E.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Departments of Medicine (S.Y.W., R.N.C., H.G., J.N., S.R., R.E.W.), Chicago Illinois 60645"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071618244742100_R1","first-page":"348","article-title":"The syndromes of resistance to thyroid hormone.","volume":"14","author":"Refetoff","year":"1993","journal-title":"Endocr Rev"},{"key":"2020071618244742100_R2","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1172\/JCI115225","article-title":"Thyroid hormone resistance syndrome. 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