Abstract
Generalized resistance to thyroid hormone (GRTH) is an inherited syndrome of reduced tissue responsiveness to thyroid hormone. Point mutations in the human thyroid hormone receptor-beta (hTR beta) gene of these patients, causing single amino acid substitutions, appear be different in unrelated individuals affected by the same syndrome. To localize mutations in the hTR beta gene, GC-clamped DNA fragments from affected individuals belonging to 21 families with GRTH were generated by the polymerase chain reaction and analyzed by denaturing gradient gel electrophoresis (DGGE). Putative mutations in the hTR beta gene of 18 unrelated individuals with GRTH were identified, and their nature has been confirmed in 9 by sequencing. All were in the hormone-binding domain of the receptor, and 13 of 18 mutations were in its center (exon 7). In 3 families we were unable to identify mutations in hTR beta, suggesting the existence of mutations at other loci, possibly the hTR alpha gene or other proteins involved in the thyroid hormone-dependent transactivation system. Sequencing of DNA fragments negative for the presence of putative mutations by DEEG confirmed the absence of sequence differences. DGGE of amplified DNA fragments can rapidly and reliably localize the sites of mutations in the hTR beta gene of patients with GRTH. The procedure enabled mapping the regions in the hTR beta harboring mutations associated with GRTH.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: Journal of Clinical Endocrinology & Metabolism
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.