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Homozygosity for a Dominant Negative Thyroid Hormone Receptor Gene Responsible for Generalized Resistance to Thyroid Hormone*

1991; Oxford University Press; Volume: 73; Issue: 5 Linguagem: Inglês

10.1210/jcem-73-5-990

1945-7197

Seigo Ono, I. David Schwartz, O. Thomas Mueller, Allen W. Root, Stephen J. Usala, Barry B. Bercu,

Hypothalamic control of reproductive hormones

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.