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SEIGO ONO, I. DAVID SCHWARTZ, O. THOMAS MUELLER, ALLEN W. ROOT, STEPHEN J. USALA, BARRY B. BERCU, Homozygosity for a Dominant Negative Thyroid Hormone Receptor Gene Responsible for Generalized Resistance to Thyroid Hormone, The Journal of Clinical Endocrinology & Metabolism, Volume 73, Issue 5, 1 November 1991, Pages 990–994, https://doi.org/10.1210/jcem-73-5-990
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Abstract
Generalized resistance to thyroid hormones (GRTH) commonly results from mutations in the T3-binding domain of the c-erbAβ thyroid hormone receptor gene. We have reported on a novel deletion mutation in c-erbAβ in a kindred, S, with GRTH. One patient from this kindred was the product of a consanguineous union from two affected members and was homozygous for the β-receptor defect. This patient at 3.5 weeks of age had unprecedented elevations of TSH, free T4, and free T3 (TSH, 389 mU/L; free T4, 330.8 pmol/L; free T3, 82,719 fmol/L). He displayed a complex mixture of tissue-specific hyperthyroidism and hypothyroidism. He had delayed growth (height age, 1 3/12 yr at chronological age 2 9/12 yr) and skeletal maturation (bone age, 4 months), and developmental delay (developmental age, 8 months), but he was quite tachycardia The homozygous patient of kindred S is markedly different from a recently reported patient with no c-erbA β-receptor. This difference indicates that a dominant negative form of c-erbAβ in man can inhibit at least some thyroid hormone action mediated by the c-erbA α-receptors.