No Mutations in the Translated Region of Exon 1 in the TSH Receptor in Graves' Thyroid Glands

Ahmad, Mir F.; Stenszky, V.; Juhazs, F.; Balázs, György; Farid, Nadir R.

doi:10.1089/thy.1994.4.151

Cited by 12 publications

(3 citation statements)

References 9 publications

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“…Extraction of genomic DNAs from the frozen tissue specimens and lymphocytes was performed using the phenol-chloroform method as described previously [31,32].…”

Section: Dna Isolationmentioning

confidence: 99%

Mutations in the Thyrotropin Receptor Signal Transduction Pathway in the Hyperfunctioning Thyroid Nodules from Multinodular Goiters: A Study in the Turkish Population

et al. 2005

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Abstract. Many studies have been carried out to determine G s a and TSHR mutations in autonomously functioning thyroid nodules. Variable prevalences for somatic constitutively activating TSHR mutations in hot nodules have been reported. Moreover, the increased prevalence of toxic multinodular goiters in iodine-deficient regions is well known. In Turkey, a country with high incidence rates of goiter due to iodine deficiency, the frequency of mutations in the thyrotropin receptor signal transduction pathway has not been evaluated up to now. In the present study, a part of the genes of the TSHR, G s a and the catalytic subunit of the PKA were checked for activating mutations. Thirty-five patients who underwent thyroidectomy for multinodular goiters were examined. Genomic DNAs were extracted from 58 hyperactive nodular specimens and surrounding normal thyroid tissues. Mutation screening was done by single-strand conformational polymorphism (SSCP) analysis. In those cases where a mutation was detected, the localization of the mutation was determined by automatic DNA sequencing. No G s a or PKA mutations were detected, whereas ten mutations (17%) were identified in the TSHR gene. All mutations were somatic and heterozygotic. In conclusion, the frequency of mutations in the cAMP signal transduction pathway was found to be lower than expected in the Turkish population most likely because of the use of SSCP as a screening method and sequencing only a part of TSHR exon 10.

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“…Extraction of genomic DNAs from the frozen tissue specimens and lymphocytes was performed using the phenol-chloroform method as described previously [31,32].…”

Section: Dna Isolationmentioning

confidence: 99%

Mutations in the Thyrotropin Receptor Signal Transduction Pathway in the Hyperfunctioning Thyroid Nodules from Multinodular Goiters: A Study in the Turkish Population

et al. 2005

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“…Genomic DNA was extracted from the frozen tissue specimens and peripheral leukocytes by using the phenol-chloroform method and stored at Ϫ20°C for future analysis (16,17). The polymerase chain reaction (PCR) was used to amplify exon 8-9 of the G s ␣ gene that contains the base substutions at codon 201 and 227 and a part of exon 10 of the TSHR gene.…”

Section: Genetic Analysismentioning

confidence: 99%

Does a Leu 512 Arg Thyrotropin Receptor Mutation Cause an Autonomously Functioning Papillary Carcinoma?

Gözü

Avşar

Bircan

et al. 2004

Thyroid

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In the last decade, studies were first done to determine the frequency of Gsalpha and later thyrotropin receptor (TSHR) mutations in benign autonomously functioning thyroid nodules (AFTN). Different frequencies ranging from 0% to 38% for GSp mutations and from 20% to 86% for TSHR mutations were found. There were only some limited case reports related to TSHR genetic alterations in malignant AFTN. Their role in autonomously functioning thyroid carcinomas is not well established. We present a patient who had thyroidectomy for toxic multinodular goiter and a papillary carcinoma was demonstrated histopathologically. Genomic DNA was isolated from two solid areas in the hot nodule and peripheral leukocytes of the patient. After amplifying the related regions, TSHR and GSalpha genes were analyzed by single-strand conformation polymorphism (SSCP) analysis. The precise localization of the mutations was identified by automatic DNA sequence analysis. An activating mutation of the TSHR gene (Leu 512 Arg) was found in the autonomously functioning papillary carcinoma. It is believed that this mutation causes constitutive activation of the cyclic adenosine monophosphate (cAMP) signal transduction pathway and thereby causes thyrotoxicosis and a hot thyroid nodule in an autonomously functioning papillary carcinoma.

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“…Genomic DNAs were isolated from hyperfunctioning thyroid nodules, normal thyroid tissues, and blood leucocytes using the phenol-chloroform method as previously described (9,10). A DNA fragment including exons 8-9 of the G s ␣ gene was amplified using primers and polymerase chain reaction (PCR) conditions as described by Spambalg et al (11).…”

Section: Genetic Analysismentioning

confidence: 99%

Two Novel Mutations in the Sixth Transmembrane Segment of the Thyrotropin Receptor Gene Causing Hyperfunctioning Thyroid Nodules

Gözü

Avşar²,

Bircan³

et al. 2005

Thyroid

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Autonomously functioning thyroid nodules (AFTNs) can present as hyperfunctioning adenomas or toxic multinodular goiters. In the last decade, a large number of activating mutations have been identified in the thyrotropin receptor (TSHR) gene in autonomously functioning thyroid nodules. Most have been situated close to, or within the sixth transmembrane segment and third intracellular loop of the TSHR where the receptor interacts with the Gs protein. In this study we describe two novel mutations in the sixth transmembrane segment of the TSHR causing hyperfunctioning thyroid nodules. Genomic DNAs were isolated from four hyperfunctioning thyroid nodules, normal tissues and peripheral leukocytes of two patients with toxic multinodular goiter. After amplifying the related regions, TSHR and G(s)alpha genes were analyzed by single-strand conformation polymorphism (SSCP) analysis. The precise localization of the mutations was identified by automatic DNA sequence analysis. Functional studies were done by site-directed mutagenesis and transfection of a mutant construct into COS-7 cells. We identified two novel TSHR mutations in two hyperfunctioning thyroid nodules: Phe631Val in the first patient and Iso630Met in the second patient. Both mutant receptors display an increase in constitutive stimulation of basal cyclic adenosine monophosphate (cAMP) levels compared to the wild-type receptor. This confirms that these mutant receptors cause hyperfunctioning thyroid nodules.

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No Mutations in the Translated Region of Exon 1 in the TSH Receptor in Graves' Thyroid Glands

Cited by 12 publications

References 9 publications

Mutations in the Thyrotropin Receptor Signal Transduction Pathway in the Hyperfunctioning Thyroid Nodules from Multinodular Goiters: A Study in the Turkish Population

Mutations in the Thyrotropin Receptor Signal Transduction Pathway in the Hyperfunctioning Thyroid Nodules from Multinodular Goiters: A Study in the Turkish Population

Does a Leu 512 Arg Thyrotropin Receptor Mutation Cause an Autonomously Functioning Papillary Carcinoma?

Two Novel Mutations in the Sixth Transmembrane Segment of the Thyrotropin Receptor Gene Causing Hyperfunctioning Thyroid Nodules

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