Resistance to TSH is a syndrome due to reduced responsiveness of the thyroid gland to biologically active TSH. Inactivating mutations of the TSH receptor (TSH-R) have been detected in several cases of resistance to TSH, both partial and complete, sporadic and familial. In this study, we describe a family with the presence of resistance to TSH responsible for euthyroid hyperthyrotropinemia in two siblings from consanguineous parents. By direct sequencing of the TSH receptor gene, we identified a new mutation responsible for the substitution of an arginine with a cysteine at position 310, in the extracellular domain of the TSH-R. The mutation was homozygous in two brothers; heterozygous in both parents, an uncle, and an unaffected brother; and absent in the other unaffected brother. When stably transfected in Chinese hamster ovary cells, the Cys310 mutant TSH-R showed loss of response to TSH in terms of cAMP stimulation. However, a constitutive activity in terms of basal cAMP production was detected in the Cys310 mutant, compared with the wild-type TSH-R. Our data suggest that such a Cys310 TSH-R mutant may determine both the TSH resistance and the clinical euthyroidism detected in this family.

A novel mutation in the thyrotropin (TSH) receptor gene causing loss of TSH binding but constitutive receptor activation in a family with resistance to TSH / Diego, Russo; Corrado, Betterle; Franco, Arturi; Eusebio, Chiefari; Maria E., Girelli; Filetti, Sebastiano. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. - ISSN 0021-972X. - 85:11(2000), pp. 4238-4242. [10.1210/jcem.85.11.6985]

A novel mutation in the thyrotropin (TSH) receptor gene causing loss of TSH binding but constitutive receptor activation in a family with resistance to TSH

FILETTI, SEBASTIANO
2000

Abstract

Resistance to TSH is a syndrome due to reduced responsiveness of the thyroid gland to biologically active TSH. Inactivating mutations of the TSH receptor (TSH-R) have been detected in several cases of resistance to TSH, both partial and complete, sporadic and familial. In this study, we describe a family with the presence of resistance to TSH responsible for euthyroid hyperthyrotropinemia in two siblings from consanguineous parents. By direct sequencing of the TSH receptor gene, we identified a new mutation responsible for the substitution of an arginine with a cysteine at position 310, in the extracellular domain of the TSH-R. The mutation was homozygous in two brothers; heterozygous in both parents, an uncle, and an unaffected brother; and absent in the other unaffected brother. When stably transfected in Chinese hamster ovary cells, the Cys310 mutant TSH-R showed loss of response to TSH in terms of cAMP stimulation. However, a constitutive activity in terms of basal cAMP production was detected in the Cys310 mutant, compared with the wild-type TSH-R. Our data suggest that such a Cys310 TSH-R mutant may determine both the TSH resistance and the clinical euthyroidism detected in this family.
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A novel mutation in the thyrotropin (TSH) receptor gene causing loss of TSH binding but constitutive receptor activation in a family with resistance to TSH / Diego, Russo; Corrado, Betterle; Franco, Arturi; Eusebio, Chiefari; Maria E., Girelli; Filetti, Sebastiano. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. - ISSN 0021-972X. - 85:11(2000), pp. 4238-4242. [10.1210/jcem.85.11.6985]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/92721
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