ArticleThe Journal of clinical investigation1994
Mutations of CpG dinucleotides located in the triiodothyronine (T3)-binding domain of the thyroid hormone receptor (TR) beta gene that appears to be devoid of natural mutations may not be detected because they are unlikely to produce the clinical phenotype of resistance to thyroid hormone.
Article in The Journal of clinical investigation, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 65 citations in OpenAlex.
- Clinical Consequences of Variable Results in the Measurement of Free Thyroid Hormones: Unusual Presentation of a Family with a Novel Variant in theEuropean thyroid journal · 2021Article
- Resistance to Thyroid Hormone Beta: A Focused Review.Frontiers in endocrinology · 2021Review
- A Novel G385E Variant in the Cold Region of the T3-Binding Domain of Thyroid Hormone Receptor Beta Gene and Investigations to Assess Its Clinical Significance.European thyroid journal · 2019Article
- A clinician's guide to understanding resistance to thyroid hormone due to receptor mutations in the TRα and TRβ isoforms.Clinical diabetes and endocrinology · 2017Article
- Characteristics of patients with late manifestation of resistance thyroid hormone syndrome: a single-center experience.Endocrine · 2015Article
- Incidental identification of a thyroid hormone receptor beta (THRB) gene variant in a family with autoimmune thyroid disease.Thyroid : official journal of the American Thyroid Association · 2013Article
- The syndromes of reduced sensitivity to thyroid hormone.Biochimica et biophysica acta · 2013Review
- Pathogenic mechanism of mutations in the thyroid hormone receptor β gene.Journal of endocrinological investigation · 2012Article
- Thyroid hormone receptor α and regulation of type 3 deiodinase.Molecular endocrinology (Baltimore, Md.) · 2011Article
- Approach to the patient with resistance to thyroid hormone and pregnancy.The Journal of clinical endocrinology and metabolism · 2010Article
- Article
- A potential role of activated NF-kappa B in the pathogenesis of euthyroid sick syndrome.The Journal of clinical investigation · 2000Article
- A role for helix 3 of the TRbeta ligand-binding domain in coactivator recruitment identified by characterization of a third cluster of mutations in resistance to thyroid hormone.The EMBO journal · 1998Article
- Congenital hypothyroidism due to mutations in the sodium/iodide symporter. Identification of a nonsense mutation producing a downstream cryptic 3' splice site.The Journal of clinical investigation · 1998Article
- Autosomal dominant postaxial polydactyly, nail dystrophy, and dental abnormalities map to chromosome 4p16, in the region containing the Ellis-van Creveld syndrome locus.American journal of human genetics · 1997Article
- A natural transactivation mutation in the thyroid hormone beta receptor: impaired interaction with putative transcriptional mediators.Proceedings of the National Academy of Sciences of the United States of America · 1997Article
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3 authors at 1 institution in 1 country.
Funding
Abstract
Thyroid hormone receptor (TR) beta gene mutations identified in patients with resistance to thyroid hormone (RTH) revealed two clusters ("hot" areas) of mutations (RTHmut) in the triiodothyronine (T3)-binding domain. Furthermore, 45% of RTHmuts and 90% of recurring mutations are located in CpG dinucleotides ("hot spots"). To investigate why the region between the two hot areas lacks RTHmuts, we produced 10 artificial mutant TR beta s (ARTmut) in this "cold" region according to the hot spot rule (C-->T or G-->A substitutions in CpGs). The properties of ARTmuts were compared with those of six RTHmuts. Among all RTHmuts, R320H manifesting a mild form of RTH showed the least impairment of T3-binding affinity (Ka). In contrast, Ka was normal in six ARTmuts (group A), reduced to a lesser extent than R320H in three (group B), and one that was truncated (R410X) did not bind T3. All RTHmuts had impaired ability to transactivate T3-responsive elements and exhibited a strong dominant negative effect on cotransfected wild-type TR beta. Group B and A ARTmuts had minimally impaired or normal transactivation and weak or no dominant negative effect, respectively. R410X showed neither transactivation nor dominant negative effect. Natural mutations expected to occur in the cold region of TR beta should fail to manifest as RTH (group A) or should escape detection (group B) since the serum thyroid hormone levels required to compensate for the reduced binding affinity should be inferior to those found in subjects with R320H. R410X would manifest RTH only in the homozygote state. The cold region of the putative T3-binding domain is relatively insensitive to amino acid changes and, thus, may not be involved in a direct interaction with T3.
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