Congenital Hypothyroidism with Impaired Thyroid Response to Thyrotropin (TSH) and Absent Circulating Thyroglobulin: Evidence for a New Inactivating Mutation of the TSH Receptor Gene

2000 ◽  
Vol 85 (3) ◽  
pp. 1001-1008 ◽  
Author(s):  
M. Tonacchera
Keyword(s):  
Congenital Hypothyroidism ◽  
Receptor Gene ◽  
Tsh Receptor ◽  
Inactivating Mutation

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.

scholarly journals Severe congenital hypothyroidism due to a novel deep intronic mutation in the TSH receptor gene causing intron retention

2020 ◽  
Author(s):  
Stéphanie Larrivée-Vanier ◽  
Fabien Magne ◽  
Elwaseila Hamdoun ◽  
Anna Petryk ◽  
Zoha Kibar ◽  
...  
Keyword(s):  
Cell Surface ◽  
Exome Sequencing ◽  
Congenital Hypothyroidism ◽  
Transmembrane Domain ◽  
Intron Retention ◽  
Receptor Gene ◽  
Tsh Receptor ◽  
Intronic Mutation ◽  
Exome Analysis ◽  
Isoform Expression

Abstract In three Somalian siblings with severe nongoitrous congenital hypothyroidism, exome sequencing identified a variant in TSHR predicted to be benign in isoform 3 but leading to an intronic mutation in isoform 1 (NM_00369:c.692 + 130C>A), which is the isoform expressed in the thyroid. This mutation creates a pseudo-exon that results in a protein that, if transcribed, would lack the transmembrane domain, thereby hampering its expression at the cell surface. Our findings illustrate that the interpretation of exome analysis requires knowledge of the relevant isoform expression and of the biology of the disease. This is the first description of a deep intronic mutation creating a pseudo-exon and inactivating the TSH receptor.

scholarly journals Congenital Hypothyroidism with Impaired Thyroid Response to Thyrotropin (TSH) and Absent Circulating Thyroglobulin: Evidence for a New Inactivating Mutation of the TSH Receptor Gene*

2000 ◽  
Vol 85 (3) ◽  
pp. 1001-1008
Author(s):  
Massimo Tonacchera ◽  
Patrizia Agretti ◽  
Aldo Pinchera ◽  
Veronica Rosellini ◽  
Anna Perri ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Congenital Hypothyroidism ◽  
Tsh Receptor ◽  
Receptor Protein ◽  
Extracellular Loop ◽  
Serum Thyroglobulin ◽  
Inactivating Mutation ◽  
First Time ◽  
Serum Tsh ◽  
Bovine Tsh

Abstract Congenital hypothyroidism due to impaired thyroid response to TSH was originally described by Stanbury. A diagnosis of congenital hypothyroidism with thyroid unresponsiveness to TSH is accepted if the patient has congenital hypothyroidism, the thyroid gland is in the normal position in the neck, the size of the thyroid is either normal or atrophic, the serum TSH level is increased, the bioactivity of TSH is intact, and the response of the thyroid gland to TSH stimulation is decreased. In all originally described cases serum thyroglobulin was undetectable. We describe a 22-yr-old female patient who was severely hypothyroid and mentally retarded. Serum T4 and T3 concentrations were below the sensitivity of the methods, with elevated serum TSH levels. Serum thyroglobulin was undetectable. A normally shaped hypoplastic gland located in the appropriate anatomical position in the neck was found at scintiscan. The gland did not respond after administration of bovine TSH in terms of 131I uptake, serum thyroid hormones, and thyroglobulin secretion. A diagnosis of congenital hypothyroidism due to TSH unresponsiveness was formulated. Genetic analysis in the propositus showed a homozygous inactivating mutation of the TSH receptor that had not been previously described. The mutation consisted of the substitution of an isoleucine in place of a highly conserved threonine at position 477 in the first extracellular loop of the receptor (T477I). The brother, one sister of the father (whose DNA was not available), the mother of the propositus, one sister, and the brother were heterozygous for T477I. All the heterozygous persons were unaffected. After transfection in COS-7 cells, the mutant receptor displayed an extremely low expression at cell surface. At variance with cells transfected with the wild-type TSH receptor, cells transfected with the mutant T477I did not show constitutive activity for the adenylyl cyclase pathway. A dramatic reduction in the amount of cAMP accumulation after bovine TSH challenge was observed in cells transfected with the mutant T477I receptor. A structural defect in the mutant TSH receptor protein was probably responsible for the poor routing of the receptor to the cell membrane. This is the first time that a loss of function mutation of the TSH receptor is described in a patient with severe congenital hypothyroidism and absent circulating thyroglobulin due to TSH unresponsiveness and the first time that an inactivating mutation of the TSH receptor is described in the first extracellular loop.

Genetic and linkage analysis of familial congenital hypothyroidism: exclusion of linkage to the TSH receptor gene

1997 ◽  
Vol 99 (2) ◽  
pp. 186-190 ◽  
Author(s):  
B. Edman Ahlbom ◽  
Muhammad Yaqoob ◽  
Agne Larsson ◽  
Adam Ilicki ◽  
Göran Annerén ◽  
...  
Keyword(s):  
Linkage Analysis ◽  
Congenital Hypothyroidism ◽  
Receptor Gene ◽  
Tsh Receptor

scholarly journals Congenital Neonatal Hyperthyroidism Caused by Germline Mutations in the TSH Receptor Gene

2008 ◽  
Vol 21 (5) ◽  
Author(s):  
J. Chester ◽  
D. Rotenstein ◽  
U. Ringkananont ◽  
G. Steuer ◽  
Β. Carlin ◽  
...  
Keyword(s):  
Receptor Gene ◽  
Germline Mutations ◽  
Tsh Receptor ◽  
Neonatal Hyperthyroidism

Prevalence of germline mutations in the TSH receptor gene as a cause of juvenile thyrotoxicosis

2007 ◽  
Vol 93 (9) ◽  
pp. 1192-1194 ◽  
Author(s):  
L Lavard ◽  
B Brock Jacobsen ◽  
H Perrild ◽  
G Vassart ◽  
J Parma
Keyword(s):  
Receptor Gene ◽  
Germline Mutations ◽  
Tsh Receptor

A Novel Mutation in the Thyrotropin (Thyroid-Stimulating Hormone) Receptor Gene in a Case of Congenital Hypothyroidism

Thyroid ◽  
2006 ◽  
Vol 16 (12) ◽  
pp. 1303-1309 ◽  
Author(s):  
A. Jeziorowska ◽  
B. Pniewska-Siark ◽  
E. Brzeziańska ◽  
D. Pastuszak-Lewandoska ◽  
A. Lewiński
Keyword(s):  
Congenital Hypothyroidism ◽  
Hormone Receptor ◽  
Novel Mutation ◽  
Receptor Gene ◽  
Thyroid Stimulating Hormone ◽  
Hormone Receptor Gene ◽  
Stimulating Hormone

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

Hypothyroidism caused by the combination of two heterozygous mutations: one in the TSH receptor gene the other in the DUOX2 gene

2015 ◽  
Vol 28 (5-6) ◽  
Author(s):  
Mari Satoh ◽  
Keiko Aso ◽  
Sayaka Ogikubo ◽  
Atsuko Yoshizawa-Ogasawara ◽  
Tsutomu Saji
Keyword(s):  
Receptor Gene ◽  
The Other ◽  
Tsh Receptor

AbstractSubjects who are heterozygous for

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