{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:07:31Z","timestamp":1783487251807,"version":"3.55.0"},"reference-count":20,"publisher":"The Endocrine Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Context: T4-binding globulin (TBG) is the main transport protein for T4 in blood and a member of the superfamily of serine proteinase inhibitors. So far, 14 mutations leading to familial complete TBG deficiency have been reported. Eleven of these are caused by mutations leading to truncation of the molecule, and three are caused by single amino acid substitutions.<\/jats:p><jats:p>Objective: We report and study the complete deficiency TBG variant found in a patient from NeuIsenburg, Germany (TBG-CDNI).<\/jats:p><jats:p>Methods: Direct DNA sequencing was used to identify the TBG-CDNI mutation in the propositus, which was confirmed by allele-specific amplification. Site-directed mutagenesis and expression in Xenopus oocytes was used to study the secretion defect of TBG-CDNI and several variants by Western blot and T4-binding assay.<\/jats:p><jats:p>Results: The deletion of two nucleotides in codon 384 (1211_1212delTC) causes a frameshift altering the last 11 residues, introduces a new glycosylation site, and elongates the molecule by seven new amino acids. In contrast to normal TBG, TBG-CDNI was not secreted by Xenopus oocytes. Elongation of normal TBG by seven alanines did not affect its secretion or binding properties. On the other hand, neither disruption of its new glycosylation site nor termination of TBG-CDNI at the normal length repaired its secretion defect.<\/jats:p><jats:p>Conclusions: In this first late termination variant of complete TBG deficiency, alteration of \u03b2-strand 5B, located in the core of the molecule, rather than elongation of the molecule or introduction of a new glycosylation site, suffices to disrupt secretion of TBG-CDNI.<\/jats:p>","DOI":"10.1210\/jc.2005-2261","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T09:00:19Z","timestamp":1149066019000},"page":"3215-3218","source":"Crossref","is-referenced-by-count":5,"title":["C-Terminal Amino Acid Alteration rather than Late Termination Causes Complete Deficiency of Thyroxine-Binding Globulin CD-NeuIsenburg"],"prefix":"10.1210","volume":"91","author":[{"given":"Lars C.","family":"Moeller","sequence":"first","affiliation":[{"name":"Division of Endocrinology (L.C.M., A.F., H.L., K.M., O.E.J.), Department of Medicine, University Hospital of Essen Medical School, 45122 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Fingerhut","sequence":"additional","affiliation":[{"name":"Division of Endocrinology (L.C.M., A.F., H.L., K.M., O.E.J.), Department of Medicine, University Hospital of Essen Medical School, 45122 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Lahner","sequence":"additional","affiliation":[{"name":"Division of Endocrinology (L.C.M., A.F., H.L., K.M., O.E.J.), Department of Medicine, University Hospital of Essen Medical School, 45122 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Grasberger","sequence":"additional","affiliation":[{"name":"Department of Medicine (H.G.), The University of Chicago, Chicago, Illinois 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Weimer","sequence":"additional","affiliation":[{"name":"Endokrinologische Gemeinschaftspraxis (B.W., J.H.), 60329 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Happ","sequence":"additional","affiliation":[{"name":"Endokrinologische Gemeinschaftspraxis (B.W., J.H.), 60329 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Mann","sequence":"additional","affiliation":[{"name":"Division of Endocrinology (L.C.M., A.F., H.L., K.M., O.E.J.), Department of Medicine, University Hospital of Essen Medical School, 45122 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onno E.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Division of Endocrinology (L.C.M., A.F., H.L., K.M., O.E.J.), Department of Medicine, University Hospital of Essen Medical School, 45122 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613462710200_R1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/BF00191811","article-title":"Precise localization of the human thyroxine-binding globulin gene to chromosome Xq22.2 by fluorescence in situ hybridization","volume":"96","author":"Mori","year":"1995","journal-title":"Hum Genet"},{"key":"2020071613462710200_R2","first-page":"428","article-title":"Localization of the human thyroxine-binding globulin gene to the long arm of the X chromosome (Xq21\u201322)","volume":"41","author":"Trent","year":"1987","journal-title":"Am J Hum Genet"},{"key":"2020071613462710200_R3","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1210\/jcem-70-3-804","article-title":"Replacement of Leu227 by Pro in thyroxine-binding globulin (TBG) is associated with complete TBG deficiency in three of eight families with this inherited defect","volume":"70","author":"Mori","year":"1990","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613462710200_R4","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1089\/105072503768499671","article-title":"An outline of inherited disorders of the thyroid hormone generating system","volume":"13","author":"Knobel","year":"2003","journal-title":"Thyroid"},{"key":"2020071613462710200_R5","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1046\/j.1365-2265.2003.01730.x","article-title":"Two novel mutations in the gene encoding thyroxine-binding globulin (TBG) as a cause of complete TBG deficiency in Taiwan","volume":"58","author":"Su","year":"2003","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071613462710200_R6","doi-asserted-by":"crossref","first-page":"13998","DOI":"10.1016\/S0021-9258(19)49669-5","article-title":"In vitro expression of thyroxine-binding globulin (TBG) variants. Impaired secretion of TBGPRO-227 but not TBGPRO-113","volume":"267","author":"Janssen","year":"1992","journal-title":"J Biol Chem"},{"key":"2020071613462710200_R7","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1507\/endocrj1954.39.577","article-title":"Thyroxine-binding globulin variant (TBG-Kumamoto): identification of a point mutation and genotype analysis of its family","volume":"39","author":"Shirotani","year":"1992","journal-title":"Endocrinol Jpn"},{"key":"2020071613462710200_R8","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/BF03348482","article-title":"Variant thyroxine-binding globulin in serum of Australian aborigines: its physical, chemical and biological properties","volume":"8","author":"Murata","year":"1985","journal-title":"J Endocrinol Invest"},{"key":"2020071613462710200_R9","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/BF03349576","article-title":"Molecular basis for the properties of the thyroxine-binding globulin-slow variant in American blacks","volume":"13","author":"Waltz","year":"1990","journal-title":"J Endocrinol Invest"},{"key":"2020071613462710200_R10","doi-asserted-by":"crossref","first-page":"28234","DOI":"10.1074\/jbc.270.47.28234","article-title":"Molecular and structural characterization of the heat-resistant thyroxine-binding globulin-Chicago","volume":"270","author":"Janssen","year":"1995","journal-title":"J Biol Chem"},{"key":"2020071613462710200_R11","first-page":"283","article-title":"A truncated thyroxine-binding globulin due to a frameshift mutation is retained within the rough endoplasmic reticulum: a possible mechanism of complete thyroxine-binding globulin deficiency in Japanese","volume":"78","author":"Miura","year":"1994","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613462710200_R12","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1210\/jcem-59-2-269","article-title":"Radioimmunoassays specific for the tertiary and primary structures of thyroxine-binding globulin (TBG): measurement of denatured TBG in serum","volume":"59","author":"Refetoff","year":"1984","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613462710200_R13","doi-asserted-by":"crossref","first-page":"15046","DOI":"10.1074\/jbc.274.21.15046","article-title":"Modularity of serpins. 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