{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T18:13:26Z","timestamp":1783448006889,"version":"3.55.0"},"reference-count":9,"publisher":"Bioscientifica","issue":"3","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":3301,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background: Thyroxine-binding globulin (TBG) is the major thyroid hormone transport protein in serum. Located on the long arm of the X chromosome, TBG (SERPINA7) gene mutations most commonly produce inherited partial TBG deficiency (TBG-PD). Objective: We report a novel TBG variant associated with TBG-PD identified in 2 different families of Ashkenazi origin residing in greater Chicago. Methods: Family 1: The proband was 12.6 years old when she presented for delayed puberty and was placed on L-T&amp;lt;sub&amp;gt;4&amp;lt;\/sub&amp;gt;. Although her serum TSH normalized, her serum T&amp;lt;sub&amp;gt;4&amp;lt;\/sub&amp;gt; remained low. Affected family members had low total T&amp;lt;sub&amp;gt;4&amp;lt;\/sub&amp;gt; and T&amp;lt;sub&amp;gt;3&amp;lt;\/sub&amp;gt;, but a normal free T&amp;lt;sub&amp;gt;4&amp;lt;\/sub&amp;gt; index, even when serum TSH concentrations were normal. Family 2: A 71-year-old male presented with a history of a nonfunctioning pituitary adenoma and normal pituitary axes except for low total T&amp;lt;sub&amp;gt;4&amp;lt;\/sub&amp;gt; and T&amp;lt;sub&amp;gt;3&amp;lt;\/sub&amp;gt;. His brother had a similar thyroid phenotype. Results: Following direct DNA sequencing, both index patients were found to carry a missense mutation in the TBG gene (c.751T&amp;gt;G) producing p.V215G. The proposita of family 1 was heterozygous and the proband in family 2 was hemizygous for the mutation. Isoelectric focusing showed no alteration in the TBG isoforms and in vitro expression demonstrated a TBG with reduced affinity for T&amp;lt;sub&amp;gt;4&amp;lt;\/sub&amp;gt;. Conclusions: We report a novel mutation in the TBG gene in 2 unrelated families that produces a molecule with reduced affinity for T&amp;lt;sub&amp;gt;4&amp;lt;\/sub&amp;gt; resulting in low serum T&amp;lt;sub&amp;gt;4&amp;lt;\/sub&amp;gt;. However, the physical properties of the mutant molecule remained unaltered as determined by isoelectric focusing.<\/jats:p>","DOI":"10.1159\/000455097","type":"journal-article","created":{"date-parts":[[2017,2,8]],"date-time":"2017-02-08T07:59:03Z","timestamp":1486540743000},"page":"138-142","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-17","source":"Crossref","is-referenced-by-count":9,"title":["A Novel Mutation in the TBG Gene Producing Partial Thyroxine-Binding Globulin Deficiency (Glencoe) Identified in 2 Families"],"prefix":"10.1530","volume":"6","author":[{"given":"Theodora","family":"Pappa","sequence":"first","affiliation":[{"name":"1Departments of Medicine, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars C.","family":"Moeller","sequence":"additional","affiliation":[{"name":"5Department of Endocrinology and Division of Laboratory Research, University Hospital Essen, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah V.","family":"Edidin","sequence":"additional","affiliation":[{"name":"4Department of Pediatrics, Feinberg School of Medicine Northwestern University, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvana","family":"Pannain","sequence":"additional","affiliation":[{"name":"1Departments of Medicine, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Refetoff","sequence":"additional","affiliation":[{"name":"1Departments of Medicine, Chicago, IL, USA"},{"name":"2Departments of Pediatrics, Chicago, IL, USA"},{"name":"3Departments of Committee on Genetics, The University of Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2017,2,2]]},"reference":[{"key":"2026070712490703800_ref1","doi-asserted-by":"crossref","unstructured":"Bartalena L: Recent achievements in studies on thyroid hormone-binding proteins. Endocr Rev 1990;11:47-64.10.1210\/edrv-11-1-472108013","DOI":"10.1210\/edrv-11-1-47"},{"key":"2026070712490703800_ref2","doi-asserted-by":"crossref","unstructured":"Hayashi Y, Mori Y, Janssen OE, Sunthornthepvarakul T, Weiss RE, Takeda K, Weinberg M, Seo H, Bell GI, Refetoff S: Human thyroxine-binding globulin gene: complete sequence and transcriptional regulation. Mol Endocrinol 1993;7:1049-1060.10.1210\/mend.7.8.82323048232304","DOI":"10.1210\/mend.7.8.8232304"},{"key":"2026070712490703800_ref3","doi-asserted-by":"crossref","unstructured":"Pappa T, Ferrara AM, Refetoff S: Inherited defects of thyroxine-binding proteins. 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