+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Rapid localization of mutations in the thyroid hormone receptor-beta gene by denaturing gradient gel electrophoresis in 18 families with thyroid hormone resistance



Rapid localization of mutations in the thyroid hormone receptor-beta gene by denaturing gradient gel electrophoresis in 18 families with thyroid hormone resistance



Journal of Clinical Endocrinology and Metabolism 74(4): 712-719



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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 041172056

Download citation: RISBibTeXText

PMID: 1548332

DOI: 10.1210/jcem.74.4.1548332


Related references

Identical mutations in unrelated families with generalized resistance to thyroid hormone occur in cytosine-guanine-rich areas of the thyroid hormone receptor beta gene. Analysis of 15 families. Journal of Clinical Investigation 91(6): 2408-2415, 1993

Three Japanese patients from two families with generalized resistance to thyroid hormone with mutations in exon 9 of the thyroid hormone receptor beta gene. Internal Medicine 40(8): 756-758, 2001

Five new families with resistance to thyroid hormone not caused by mutations in the thyroid hormone receptor beta gene. Journal of Clinical Endocrinology and Metabolism 84(11): 3919-3928, 1999

Screening of nineteen unrelated families with generalized resistance to thyroid hormone for known point mutations in the thyroid hormone receptor beta gene and the detection of a new mutation. Journal of Clinical Investigation 87(2): 496-502, 1991

Nomenclature of thyroid hormone receptor beta-gene mutations in resistance to thyroid hormone: consensus statement from the first workshop on thyroid hormone resistance, July 10-11, 1993, Cambridge, United Kingdom. Journal of Clinical Endocrinology and Metabolism 78(4): 990-993, 1994

Nomenclature of thyroid hormone receptor-beta gene mutations in resistance to thyroid hormone: consensus statement from the First Workshop on Thyroid Hormone Resistance, 10-11th July 1993, Cambridge, UK. European Journal of Endocrinology 130(4): 426-428, 1994

Nomenclature of thyroid hormone receptor beta gene mutations in resistance to thyroid hormone: consensus statement from the first workshop on thyroid hormone resistance, July 10-11th 1993, Cambridge, U.K. Thyroid 4(1): 135-137, 1994

Detection of thyroid-stimulating hormone receptor and Gsalpha mutations: in 75 toxic thyroid nodules by denaturing gradient gel electrophoresis. Journal of Molecular Medicine 78(12): 684-691, 2001

Nomenclature of thyroid hormone receptor beta gene mutations in resistance to thyroid hormone: consensus statement from the First Workshop on Thyroid Hormone Resistance, 10-11 July 1993, Cambridge, UK. Clinical Endocrinology 40(5): 697-700, 1994

Nomenclature of thyroid hormone receptor beta gene mutations in resistance to thyroid hormone. First workshop on thyroid hormone resistance, July 10-11, 1993, Cambridge, U.K. Journal of Endocrinological Investigation 17(4): 283-287, 1994

Correlations of language abnormalities with localization of mutations in the beta-thyroid hormone receptor in 13 kindreds with generalized resistance to thyroid hormone: identification of four new mutations. Journal of Clinical Endocrinology and Metabolism 75(4): 1039-1045, 1992

Search for abnormalities of nuclear corepressors, coactivators, and a coregulator in families with resistance to thyroid hormone without mutations in thyroid hormone receptor beta or alpha genes. Journal of Clinical Endocrinology and Metabolism 85(10): 3609-3617, 2000

Three novel mutations of thyroid hormone receptor beta gene in unrelated patients with resistance to thyroid hormone: two mutations of the same codon (H435L and H435Q) produce separate subtypes of resistance. Journal of Clinical Endocrinology and Metabolism 80(12): 3613-3616, 1995

Nomenclature of thyroid hormone receptor- gene mutations in resistance to thyroid hormone: consensus statement from the First Workshop on Thyroid Hormone Resistance, 10-11th July 1993, Cambridge, Uk. European Journal of Endocrinology 130(4): 426-428, 1994

An identical neo-mutation in the thyroid hormone receptor beta gene (A317T) in 2 unrelated Thai families with resistance to thyroid hormone. Journal of the Medical Association of Thailand 83(2): 139-145, 2000