R450H TSH receptor mutation in congenital hypothyroidism in Taiwanese children

2012 ◽  
Vol 413 (11-12) ◽  
pp. 1004-1007 ◽  
Author(s):  
Wei-Chiao Chang ◽  
Cheng-Yu Liao ◽  
Wei-Chiao Chen ◽  
Yung-Ching Fan ◽  
Siou-Jin Chiu ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Tsh Receptor ◽  
Tsh Receptor Mutation

Molecular screening of the TSH receptor (TSHR) and thyroid peroxidase (TPO) genes in Korean patients with nonsyndromic congenital hypothyroidism

2011 ◽  
Vol 75 (5) ◽  
pp. 715-721 ◽  
Author(s):  
Seung-Tae Lee ◽  
Dong Hwan Lee ◽  
Ji-Youn Kim ◽  
Min-Jung Kwon ◽  
Jong-Won Kim ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Tsh Receptor ◽  
Thyroid Peroxidase ◽  
Molecular Screening ◽  
Korean Patients

Current questions of thyroid diseases in childhood

2011 ◽  
Vol 152 (16) ◽  
pp. 617-627
Author(s):  
István Ilyés
Keyword(s):  
Congenital Hypothyroidism ◽  
Iodine Deficiency ◽  
Remission Rate ◽  
Receptor Gene ◽  
The United States ◽  
Thyroid Diseases ◽  
Tsh Receptor ◽  
First Choice ◽  
Definitive Therapy ◽  
Frequent Relapses

In recent years our knowledge on thyroid diseases in childhood has been increased. Several forms of congenital hypothyroidism (dysgenesis, dyshormongenesis, thyrotropin resistance and some central forms) are consequences of gene mutations. Maternal hypothyroxinemia due to severe iodine deficiency leads to early neurological damage and congenital hypothyroidism. Neonatal screening of congenital hypothyroidism and early treatment with l-thyroxin ensure good prognosis. Differential diagnosis of the various forms of congenital hypothyroidism in newborns is not an easy task. The need for treatment of transient hypothyroxinemia is still controversial. Diagnosis of juvenile lymphocytic thyroiditis can be ascertained by the clinical status, ultrasound examination, detection of anti-peroxydase antibodies, evaluation of thyroid function, and fine needle aspiration cytology. L-thyroxin therapy is recommended in cases of subclinical and manifest hypothyroidism. The transient form of the rare newborn hyperthyroidism is the consequence of maternal Graves-Basedow disease. It can be a sever condition and its permanent form is caused by TSH-receptor gene mutation. In the pathogenesis of autonomic thyroid adenoma mutations of the TSH-receptor and the alpha subunit of the stimulatory G-protein are involved. Treatment of Graves-Basedow disease in childhood is a debated question. The first choice is medical treatment with antithyroid and beta-blocking drugs. However, remission rate is low under this therapy, and the disease is characterised by frequent relapses. For this reason, the necessity of definitive therapy frequently arises. In Europe subtotal thyroidectomy is used as second choice of therapy, but clinical experience in the United States showed that radioiodine treatment is a safe and effective therapy for children and adolescents. Iodine deficient goitre in childhood is a form of iodine deficiency disorder. It is the consequence of adaptation to iodine deficiency. It can be treated by iodine or/and l-thyroxin, and its development can be prevented by iodinated salt. In childhood, thyroid nodule needs for a detailed investigation because of the possibility of thyroid cancer. Medullar thyroid carcinoma indicates genetic screening in the patients and their family, and the presence of disease-causing RET-proto-oncogene mutation confirms the need for total thyroidectomy already in childhood. Orv. Hetil., 2011, 152, 617–627.

Maternal TSH-Receptor Antibodies and TSH Antibodies in Screening for Congenital Hypothyroidism

1986 ◽  
Vol 75 (5) ◽  
pp. 756-761 ◽  
Author(s):  
F. A. KARLSSON ◽  
P. A. DAHLBERG ◽  
J. ALM ◽  
A. LARSSON ◽  
I. FELDING
Keyword(s):  
Congenital Hypothyroidism ◽  
Tsh Receptor ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies

The TSH receptor mutation database

1999 ◽  
pp. VII ◽  
Author(s):  
B Trultzsch ◽  
T Nebel ◽  
R Paschke
Keyword(s):  
Tsh Receptor ◽  
Mutation Database ◽  
Tsh Receptor Mutation

Inactivation of a Frameshift TSH Receptor Variant Val711Phefs*18 is Due to Acquisition of a Hydrophobic Degron

2020 ◽  
Vol 106 (1) ◽  
pp. e265-e272
Author(s):  
Chiho Sugisawa ◽  
Makoto Ono ◽  
Kenichi Kashimada ◽  
Tomonobu Hasegawa ◽  
Satoshi Narumi
Keyword(s):  
Amino Acid ◽  
Congenital Hypothyroidism ◽  
Fluorescent Protein ◽  
Transmembrane Domain ◽  
Tsh Receptor ◽  
Hek293 Cells ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Tail Region

Abstract Context Inactivating variants of thyrotropin (thyroid-stimulating hormone; TSH) receptor (TSHR) cause congenital hypothyroidism. More than 60 such variants have been reported so far, most of which were located in the extracellular or transmembrane domain. Objective We report the identification and characterization of a frameshift TSHR variant in the intracytoplasmic C-tail region. Methods Sequencing of TSHR was performed in a patient with congenital hypothyroidism. The functionality of the identified variants was assessed by expressing TSHR in HEK293 cells and measuring TSH-dependent activation of the cAMP–response element-luciferase reporter. A series of systematic mutagenesis experiments were performed to characterize the frameshifted amino acid sequence. Results The proband was heterozygous for a known TSHR variant (p.Arg519His) and a novel frameshift TSHR variant (p.Val711Phefs*18), which removed 54 C-terminal residues and added a 17–amino acid frameshifted sequence. The loss of function of Val711Phefs*18-TSHR was confirmed in vitro, but the function of Val711*-TSHR was found to be normal. Western blotting showed the low protein expression of Val711Phefs*18-TSHR. Fusion of the frameshift sequence to green fluorescent protein or luciferase induced inactivation of them, indicating that the sequence acted as a degron. A systematic mutagenesis study revealed that the density of hydrophobic residues in the frameshift sequence determined the stability. Eight additional frameshift TSHR variants that covered all possible shifted frames in C-tail were created, and another frameshift variant (Thr748Profs*27) with similar effect was found. Conclusions We characterized a naturally occurring frameshift TSHR variant located in C-tail, and provided a unique evidence that hydrophobicity in the C-terminal region of the receptor affects protein stability.

scholarly journals The First Activating TSH Receptor Mutation in Transmembrane Domain 1 Identified in a Family with Nonautoimmune Hyperthyroidism

2001 ◽  
Vol 86 (9) ◽  
pp. 4429-4433 ◽  
Author(s):  
Heike Biebermann ◽  
Torsten Schöneberg ◽  
Claudia Hess ◽  
John Germak ◽  
Thomas Gudermann ◽  
...  
Keyword(s):  
Transmembrane Domain ◽  
Tsh Receptor ◽  
Tsh Receptor Mutation

scholarly journals Detection of an Activating Mutation of the Thyrotropin Receptor in a Case of an Autonomously Hyperfunctioning Thyroid Insular Carcinoma1

1997 ◽  
Vol 82 (3) ◽  
pp. 735-738 ◽  
Author(s):  
Diego Russo ◽  
Salvatore Tumino ◽  
Franco Arturi ◽  
Paolo Vigneri ◽  
Giuseppe Grasso ◽  
...  
Keyword(s):  
Lymph Node ◽  
Receptor Gene ◽  
Tsh Receptor ◽  
Base Substitution ◽  
Thyrotropin Receptor ◽  
Malignant Phenotype ◽  
Node Metastasis ◽  
Activating Mutation ◽  
Well Differentiated ◽  
Tsh Receptor Mutation

Abstract Thyroid carcinomas, even when well differentiated, usually appear as hypofunctioning at scintigraphy. We report a case of an aggressive insular thyroid carcinoma presenting as an autonomously functioning thyroid nodule and causing severe thyrotoxicosis. The tumor was metastatic to a cervical lymph node and both lungs. An activating mutation of the TSH receptor gene in both the primary tumor and the lymph node metastasis was found, due to a base substitution at codon 633 (normal guanine at position 1896 replaced by cytosine CAC for GAC causing aspartic acid substitution by histidine). Other known oncogenes (gsp, ras, PTC/ret, trk, met, and p53) were not involved. This is the first description of an activating TSH receptor mutation in a thyroid hyperfunctioning carcinoma in which an aggressive malignant phenotype coexisted with activation of the cAMP cascade and differentiated thyroid functions.

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