Document Detail

Extreme thyroid hormone resistance in a patient with a novel truncated TR mutant.
MedLine Citation:
PMID:  11701667     Owner:  NLM     Status:  MEDLINE    
Resistance to thyroid hormone (RTH) is a syndrome in which patients have elevated thyroid hormone (TH) levels and decreased sensitivity to its action. We describe a child with extreme RTH and a severe phenotype. A 22-month-old female presented to the NIH with goiter, growth retardation, short stature, and deafness. Additionally, the patient had hypotonia, mental retardation, visual impairment, and a history of seizures. Brain magnetic resonance imaging showed evidence of demyelination and bilateral ventricular enlargement. The patient had markedly elevated free T3 and free T4 levels of more than 2000 pg/dl (normal, 230-420 pg/dl) and more than 64 pmol/liter (normal, 10.3-20.6 pmol/liter), respectively, and TSH of 6.88 mU/liter (normal, 0.6-6.3 mU/liter). These are the highest TH levels reported for a heterozygous RTH patient. A T3 stimulation test confirmed the diagnosis of RTH in the pituitary and peripheral tissues. Molecular analyses of the patient's genomic DNA by PCR identified a single base deletion in exon 10 of her TRbeta gene that resulted in a frameshift and early stop codon. This, in turn, encoded a truncated receptor that lacked the last 20 amino acids. Cotransfection studies showed that the mutant TR was transcriptionally inactive even in the presence of 10(-6) M T3 and had strong dominant negative activity over the wild-type receptor. It is likely that the severely defective TRbeta mutant contributed to the extreme RTH phenotype and resistance in our patient.
S A Phillips; P Rotman-Pikielny; J Lazar; S Ando; P Hauser; M C Skarulis; F Brucker-Davis; P M Yen
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Publication Detail:
Type:  Case Reports; Journal Article    
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  86     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-11-09     Completed Date:  2001-12-13     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5142-7     Citation Subset:  AIM; IM    
Diabetes and Molecular Regulation and Neuroendocrinology Sections, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
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MeSH Terms
Bone Development / physiology
Brain / pathology
Cells, Cultured
Frameshift Mutation
Gene Deletion
Magnetic Resonance Imaging
Thyroid Hormone Resistance Syndrome / genetics*
Thyroxine / blood
Transcription, Genetic / genetics
Triiodothyronine / blood,  diagnostic use
Reg. No./Substance:
6893-02-3/Triiodothyronine; 7488-70-2/Thyroxine

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