Congenital hyperthyroidism caused by a solitary toxic adenoma harboring a novel somatic mutation (serine281-->isoleucine) in the extracellular domain of the thyrotropin receptor.

Details

Serval ID
serval:BIB_323063773B5C
Type
Article: article from journal or magazin.
Collection
Publications
Title
Congenital hyperthyroidism caused by a solitary toxic adenoma harboring a novel somatic mutation (serine281-->isoleucine) in the extracellular domain of the thyrotropin receptor.
Journal
The Journal of clinical investigation
Author(s)
Kopp P., Muirhead S., Jourdain N., Gu W.X., Jameson J.L., Rodd C.
ISSN
0021-9738 (Print)
ISSN-L
0021-9738
Publication state
Published
Issued date
15/09/1997
Peer-reviewed
Oui
Volume
100
Number
6
Pages
1634-1639
Language
english
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Abstract
Activating somatic mutations in the thyrotropin (TSH) receptor have been identified as a cause of hyperfunctioning thyroid adenomas, and germline mutations have been found in familial nonautoimmune hyperthyroidism and sporadic congenital hyperthyroidism. All mutations reported to date have been located in the transmembrane domain. We now report an example of an activating mutation in the extracellular, TSH-binding domain, found in a male infant with congenital hyperthyroidism due to a toxic adenoma. The pregnancy was remarkable for fetal tachycardia. Scintigraphic studies demonstrated a large nodule in the right lobe, and a hemithyroidectomy was performed at the age of 2 yr. Direct sequencing of the TSH receptor gene revealed a mutation in one allele resulting in a substitution of serine281 by isoleucine (Ser281--> Ile) in the extracellular domain. The mutation was restricted to the adenomatous tissue. Expression of the Ser281--> Ile mutation in vitro revealed an increase in basal cAMP levels. Affinity for TSH was increased by the mutation. These findings demonstrate that activating mutations can also occur in the extracellular domain of the TSH receptor, and support a model in which the extracellular domain serves to restrain receptor function in the absence of TSH or antibody-induced conformational changes.
Keywords
Adenoma/diagnostic imaging, Adenoma/genetics, Adenoma/parasitology, Cells, Cultured, Cyclic AMP/metabolism, Humans, Hyperthyroidism/genetics, Infant, Newborn, Isoleucine/genetics, Male, Mutation, Radionuclide Imaging, Receptors, Thyrotropin/genetics, Serine/genetics, Technetium Compounds, Thyroid Neoplasms/diagnostic imaging, Thyroid Neoplasms/genetics, Thyroid Neoplasms/pathology, Thyrotropin/pharmacology, Transfection, Ultrasonography
Pubmed
Web of science
Open Access
Yes
Create date
30/12/2020 16:36
Last modification date
31/12/2020 7:26
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