A novel thyroid hormone receptor-beta mutation that fails to bind nuclear receptor corepressor in a patient as an apparent cause of severe, predominantly pituitary resistance to thyroid hormone

Basit Öğe Kaydı
dc.contributor.authorWu, Sharon Y.
dc.contributor.authorCohen, Ronald N.
dc.contributor.authorŞimşek, Enver
dc.contributor.authorŞenses, Dursun A.
dc.contributor.authorYar, Neşe E.
dc.contributor.authorGrasberger, Helmut
dc.contributor.authorWeiss, Roy E.
dc.date.accessioned2020-04-30T22:38:48Z
dc.date.available2020-04-30T22:38:48Z
dc.date.issued2006
dc.departmentDÜ, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümüen_US
dc.descriptionLahiri, Sharon/0000-0003-0678-6262en_US
dc.descriptionWOS: 000237330000042en_US
dc.descriptionPubMed: 16464943en_US
dc.description.abstractContext: Resistance to thyroid hormone ( RTH) is a dominantly inherited syndrome of variable tissue hyporesponsiveness to thyroid hormone ( TH). Objective: We report a newborn who presented with severe RTH ( Mkar) with serum TSH 1500 mU/ liter and free T-3 greater than 50 p(M) ( normal 3.1 - 9.4) and free T-4 25.3 pM ( normal 12 - 22). We hypothesized that the RTH was due to reduced ligand binding and/ or abnormal interaction with nuclear cofactors. Design: These were prospective in vivo and in vitro studies. Setting: The study was conducted at a tertiary care university hospital. Patients: Patients included a newborn child and two other subjects with RTH. 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. Main Outcome Measures: Sequencing of the TH receptor ( TR)beta and in vitro measurements of receptor- cofactor interaction were measured. Results: Sequencing of the TR beta demonstrated a de novo heterozygous mutation, 1590_ 1591insT, resulting in a frameshift producing a mutant TR beta( mutTR)-beta 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 beta frameshift mutations in the carboxyl terminus. EMSA demonstrated that the Mkar mutTR beta 1 had impaired ability to recruit nuclear receptor corepressor but intact association with silencing mediator of retinoid and thyroid receptor ( SMRT). Conclusion: Our data suggest that alterations in codons 436 - 453 in helix 11 result in significantly diminished association with nuclear eceptor corepressor but not SMRT. This novel mutTR beta demonstrates nuclear corepressor specificity that results in severe predominantly pituitary RTH due to impaired release of SMRT.en_US
dc.description.sponsorshipNCRR NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR) [RR00055, RR18372]; NIDDK NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [DK15070, DK07011]en_US
dc.identifier.doi10.1210/jc.2005-2428en_US
dc.identifier.endpage1895en_US
dc.identifier.issn0021-972X
dc.identifier.issn1945-7197
dc.identifier.issue5en_US
dc.identifier.startpage1887en_US
dc.identifier.urihttps://doi.org/10.1210/jc.2005-2428
dc.identifier.urihttps://hdl.handle.net/20.500.12684/2451
dc.identifier.volume91en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherEndocrine Socen_US
dc.relation.ispartofJournal Of Clinical Endocrinology & Metabolismen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.titleA novel thyroid hormone receptor-beta mutation that fails to bind nuclear receptor corepressor in a patient as an apparent cause of severe, predominantly pituitary resistance to thyroid hormoneen_US
dc.typeArticleen_US

Dosyalar

Orijinal paket
Listeleniyor 1 - 1 / 1
Küçük Resim
İsim:
2451.pdf
Boyut:
509.98 KB
Biçim:
Adobe Portable Document Format
Açıklama:
Tam Metin / Full Text
İndir

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
Makale Koleksiyonu
PubMed İndeksli Yayınlar Koleksiyonu