Document Detail

A family with a novel TSH receptor activating germline mutation (p.Ala485Val).
MedLine Citation:
PMID:  18175146     Owner:  NLM     Status:  MEDLINE    
Autosomal dominant nonautoimmune hyperthyroidism (ADNAH) is caused by gain of function mutations in the TSH receptor (TSHr) gene and characterized by toxic thyroid hyperplasia with a variable age of onset in the absence of thyroid antibodies and clinical symptoms of autoimmune thyroid disease in at least two generations. We report here a Turkish family with a novel TSHr gene mutation with distinct features all consistent with ADNAH. Thyroid function tests of the proband were as follows: free T3: 13.1 pg/ml (N: 1.8-4.6); free T4: 5.1 ng/dl (N: 0.9-1.7); TSH: 0.01 microIU/ml (N: 0.2-4.2); and TSH receptor antibody: 2 IU/ml (N: 0-10). A heterozygous missense mutation in exon 10 of the TSHr gene (c.1454C>T) resulting in the substitution of valine for alanine at codon 485 (p.Ala485Val) was found in the father and his son and daughter. This mutation had arisen de novo in the father. Functional studies of the novel TSHr germline mutation demonstrated a higher constitutive activation of adenyl cyclase than wild type without any effect on phospholipase C activity. In conclusion, our data indicate that gain of function germline mutations in the TSHr gene should be investigated in families with members suffering from thyrotoxicosis and progressive growth of goiter, but without clinical and biochemical evidence of autoimmune thyroid disease. In addition, patients harboring the same mutation of the TSHr gene may show wide phenotypic variability with respect to the age at onset, and severity of hyperthyroidism and thyroid growth.
Sema Akcurin; Doga Turkkahraman; Carolyn Tysoe; Sian Ellard; Anne De Leener; Gilbert Vassart; Sabine Costagliola
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Publication Detail:
Type:  Case Reports; Journal Article     Date:  2008-01-04
Journal Detail:
Title:  European journal of pediatrics     Volume:  167     ISSN:  1432-1076     ISO Abbreviation:  Eur. J. Pediatr.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-09-16     Completed Date:  2009-03-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603873     Medline TA:  Eur J Pediatr     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1231-7     Citation Subset:  IM    
Department of Pediatric Endocrinology, Akdeniz University Hospital, Antalya, Turkey.
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MeSH Terms
Child, Preschool
Cyclic AMP / metabolism
Gene Expression / genetics
Germ-Line Mutation / genetics*
Hyperthyroidism / enzymology,  genetics*
Immunoglobulins, Thyroid-Stimulating / immunology
Infant, Newborn
Iodide Peroxidase / metabolism
Point Mutation / genetics
Polymerase Chain Reaction
Polymorphism, Single Nucleotide / genetics
Receptors, Thyrotropin / genetics*,  immunology
Thyroxine / blood
Transfection / methods
Triiodothyronine / blood
Valine / metabolism
Reg. No./Substance:
0/Immunoglobulins, Thyroid-Stimulating; 0/Receptors, Thyrotropin; 60-92-4/Cyclic AMP; 6893-02-3/Triiodothyronine; 7004-03-7/Valine; 7488-70-2/Thyroxine; EC Peroxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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