Linked Life Data

10720030

Source:http://linkedlifedata.com/resource/pubmed/id/10720030

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-3-30
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-972X
pubmed:author
pubmed:issnType
Print
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1001-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10720030-Adult, pubmed-meshheading:10720030-Amino Acid Substitution, pubmed-meshheading:10720030-Animals, pubmed-meshheading:10720030-COS Cells, pubmed-meshheading:10720030-Cattle, pubmed-meshheading:10720030-Cercopithecus aethiops, pubmed-meshheading:10720030-Congenital Hypothyroidism, pubmed-meshheading:10720030-Female, pubmed-meshheading:10720030-Humans, pubmed-meshheading:10720030-Hypothyroidism, pubmed-meshheading:10720030-Iodine Radioisotopes, pubmed-meshheading:10720030-Mutation, pubmed-meshheading:10720030-Pedigree, pubmed-meshheading:10720030-Polymerase Chain Reaction, pubmed-meshheading:10720030-Receptors, Thyrotropin, pubmed-meshheading:10720030-Thyroglobulin, pubmed-meshheading:10720030-Thyrotropin, pubmed-meshheading:10720030-Thyroxine, pubmed-meshheading:10720030-Transfection, pubmed-meshheading:10720030-Triiodothyronine
pubmed:year
2000
pubmed:articleTitle
Congenital hypothyroidism with impaired thyroid response to thyrotropin (TSH) and absent circulating thyroglobulin: evidence for a new inactivating mutation of the TSH receptor gene.
pubmed:affiliation
Dipartimento di Endocrinologia, Università di Pisa, Italy. mtonacchera@hotmail.com
pubmed:publicationType
Journal Article, Case Reports, Research Support, Non-U.S. Gov't