Polymorphism of a Variant Human Thyrotropin Receptor (hTSHR) Gene

Sunthornthepvarakul, Thongkum; Hayashi, Yoshitaka; Refetoff, Samuel

doi:10.1089/thy.1994.4.147

Cited by 44 publications

(26 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the (Pro52Thr) variant was firstly reported by Bohr [31] and believed to have an effect on Graves' disease. In another study, Sunthornthepvaraku [32] showed the (Pro52Thr) variant was a polymorphism. It was found in 12% of the normal individuals studied and not linked to any thyroid abnormalities.…”

Section: Discussionmentioning

confidence: 94%

Thyrotropin Receptor and Thyroid Transcription Factor-1 Genes Variant in Chinese Children with Congenital Hypothyroidism

et al. 2008

View full text Add to dashboard Cite

Abstract. The aim of the present study was to investigate the mutation/variant of thyrotropin receptor (TSHR) and thyroid transcription factor-1 (TTF-1) genes in Chinese children with congenital hypothyroidism (CH). Seventy-nine and forty-nine Chinese children with CH were enrolled for molecular analysis of the TSHR gene and TTF-1 gene, respectively. One hundred normal children were evaluated as control. The coding regions of TSHR and TTF-1 genes were amplified by polymerase chain reaction and sequenced. Sequencing of the TSHR gene revealed a compound heterozygous variants (Pro52Thr/Val689Gly) and a heterozygous variant (Gly245Ser) in 2 of 79 patients. In 30 patients and 33 controls the normal cytosine at position 2181 in exon 10 of TSHR gene was replaced by a guanine， resulting in the replacement of Asp 727 by Glu. In 47 patients and 50 controls, the normal thymidine at position 561 in exon 7 of TSHR gene was replaced by a cytosine. This substitution did not change the amino acid in position 187. Sequencing of the TTF-1 gene revealed no mutation or polymorphism in 49 patients and 100 controls. In conclusion, three heterozygous variants (Pro52Thr, Gly245Ser, Val689Gly) of TSHR gene were firstly detected in Chinese children with CH. There were polymorphisms in exon 10 at nucleotide 2181 (C/G) and in exon 7 at nucleotide 561 (T/C) in TSHR gene. No mutation or polymorphism was detected in the coding region of TTF-1 gene. The mutation/variant of TSHR and TTF-1 genes is relatively rare in Chinese children with CH.

show abstract

Section: Discussionmentioning

confidence: 94%

Thyrotropin Receptor and Thyroid Transcription Factor-1 Genes Variant in Chinese Children with Congenital Hypothyroidism

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Conversely, germline loss-of-function TSHR mutations are associated with TSH resistance and congenital hypothyroidism (see reference (8) for an illustrative example). However, only three germline TSHR polymorphisms, resulting in amino acid substitutions, have been identified (9)(10)(11). Two of these are located in the extracellular domain of the receptor (Asp36His and Pro52Thr) (9,10), and one is located in the intracellular domain (Asp727Glu) (11) (Fig.…”

Section: Polymorphisms In the Tsh Receptormentioning

confidence: 99%

Genetic variation in thyroid hormone pathway genes; polymorphisms in the TSH receptor and the iodothyronine deiodinases

2006

View full text Add to dashboard Cite

Serum thyroid parameters show substantial inter-individual variability, in which genetic variation is a major factor. Findings in patients with subclinical hyper-and hypothyroidism illustrate that even minor alterations in serum thyroid function tests can have important consequences for a variety of thyroid hormone-related clinical endpoints, such as atherosclerosis, bone mineral density, obesity, and heart rate. In the last few years, several studies described polymorphisms in thyroid hormone pathway genes that alter serum thyroid function tests. In this review, we discuss the genetic variation in the TSH receptor and iodothyronine deiodinases. We discuss the possible consequences of these studies for the individual patient and also the new insights in thyroid hormone action that can be obtained from these data.European Journal of Endocrinology 155 655-662

show abstract

“…The response to bioactive TSH may be impaired at the level of the thyrocyte (figure 2) (33)(34)(35). Total insensitivity to TSH results in a small hypoplastic thyroid gland and reduced synthesis and secretion of thyroid hormones.…”

Section: Resistance To Tshmentioning

confidence: 99%

“…In partial resistance, TSH levels are elevated, but the peripheral hormones are normal, a constellation referred to as euthyroid hyperthyrotropinemia (33). In these patients, the size of the thyroid is normal or enlarged.…”

Section: Tsh Receptormentioning

confidence: 99%

Thyroglobulin gene mutations and other genetic defects associated with congenital hypothyroidism

Vono-Toniolo

Kopp

2004

Arq Bras Endocrinol Metab

View full text Add to dashboard Cite

Congenital hypothyroidism affects about 1:3000-1:4000 infants. Screening programs now permit early recognition and treatment, thus avoiding the disastrous consequences of thyroid hormone deficiency on brain development. In about 85%, congenital hypothyroidism is associated with developmental defects referred to as thyroid dysgenesis. They include thyroid (hemi)agenesis, ectopic tissue and thyroid hypoplasia. Thyroid dysgenesis is usually sporadic; in only 2% it occurs in a familial fashion. It can be caused by mutations in transcription factors that are essential for the development and function of thyroid follicular cells. Thyroid hypoplasia can also result from resistance to TSH at the level of the thyrocytes. Defects in the steps required for thyroid hormone synthesis within thyroid follicular cells are referred to as dyshormonogenesis and account for about 10-15% of congenital hypothyroidism. In contrast to thyroid dysgenesis, affected patients typically present with goitrous enlargement of the thyroid. The defects leading to dyshormonogenesis typically display a recessive mode of inheritance. Careful clinical, biochemical and molecular analyses of patients with syndromic and nonsyndromic forms of thyroid dysgenesis and dyshormonogenesis have significantly enhanced our understanding of the wide spectrum of pathogenetic mechanisms underlying congenital hypothyroidism and provide unique insights into the (patho)physiology of thyroid development and hormone synthesis. RESUMO Mutações no Gene da Tireoglobulina e Outros Defeitos Genéticos Associados Com Hipotireoidismo Congênito.Hipotireoidismo congênito afeta cerca de 1:3.000-1:4.000 recém-nascidos. Atualmente, programas de triagem neonatal permitem o reconhecimento e tratamento precoces, evitando suas conseqüências desastrosas no desenvolvimento cerebral. Em cerca de 85% dos pacientes, o hipotireoidismo congênito está associado à defeitos no desenvolvimento da tireóide referidos como disgenesia tireoideana. A disgenesia tireoideana ocorre geralmente de forma esporádica; somente 2% dos casos apresentam caráter familial. Podem ser causados por mutações nos fatores de transcrição que são essenciais para o desenvolvimento e função das células foliculares tireoideanas. Hipoplasia da tireóide pode também resultar de resistência tireoideana ao TSH. Defeitos na síntese dos hormônios tireoideanos são referidos como disormonogênese tireoideana e concorrem para 10-15% dos casos de hipotireoidismo congênito. Os pacientes usualmente apresentam bócio, ao contrário da disgenesia tireoideana. Tipicamente, os defeitos que causam disormonogênese apresentam herança recessiva. Uma série de estudos recentes aumentou significativamente nosso entendimento dos mecanismos patogênicos do hipotireoidismo congênito, oferecendo

show abstract

Polymorphism of a Variant Human Thyrotropin Receptor (hTSHR) Gene

Cited by 44 publications

References 11 publications

Thyrotropin Receptor and Thyroid Transcription Factor-1 Genes Variant in Chinese Children with Congenital Hypothyroidism

Thyrotropin Receptor and Thyroid Transcription Factor-1 Genes Variant in Chinese Children with Congenital Hypothyroidism

Genetic variation in thyroid hormone pathway genes; polymorphisms in the TSH receptor and the iodothyronine deiodinases

Thyroglobulin gene mutations and other genetic defects associated with congenital hypothyroidism

Contact Info

Product

Resources

About