Identification of four novel mutations in the thyroid hormone receptor-β gene in 164 Spanish and 2 Greek patients with resistance to thyroid hormone
The aim of the study was to describe the clinical, biochemical, and genetic features of a sample of Mediterranean patients with RTH (resistance to thyroid hormone) due to mutations in TRβ (thyroid hormone receptor beta) referred to our institution during the last 15 years.
166 blood samples were received for RTH genetic testing between January 1997 and December 2011. Genetic testing was performed by PCR amplification followed by sequencing of exons 7, 8, 9, and 10. Clinical and biochemical features were obtained from available information sent by referring hospitals.
Mutations were identified in 50 patients (29 probands and 21 relatives). 64% were women, and mean±stdev age at diagnosis among probands was 33.2±20.5 years. The following clinical features were recorded: goiter in 50%, hyperkinetic behavior in 32%, and tachycardia in 29%. Up to 19% of the probands had undergone some type of thyroidal ablative therapy before diagnosis. As for biochemical features, mean±stdev TSH was 10.2±21.4 mUI/L, and mean±stdev fT4 was 35.5±10.8 pmol/L. We found four new mutations: p.Phe451Leu, p.Pro452Arg, p.Glu457Gly, and p.Phe459Leu.
The clinical and biochemical characteristics of our samples of Mediterranean populations with RTH were similar to those described in the published literature. Interestingly, in our populations we have identified four novel mutations in the TRβ gene.
Key wordsMediterranean populations Resistance to thyroid hormone Thyroid hormone receptor-β gene mutations
Unable to display preview. Download preview PDF.
- 11.Van Mullem A, van Heerebeek R, Chrysis D, et al, 2012 Clinical Phenotype Associated with Mutation of Thyroid Hormone Receptor-α1 (TRαl). Endocr Rev 2: 33(03_MeetingAbstracts): OR26-1.Google Scholar
- 12.Adams M, Matthews C, Collingwood TN, Tone Y, Beck-Peccoz P, Chatterjee KK, 1994 Genetic analysis of 29 kindreds with generalized and pituitary resistance to thyroid hormone. Identification of thirteen novel mutations in the thyroid hormone receptor beta gene. J Clin invest 94: 506–515.CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Vlaeminck-Guillem V, Margotat A, Torresani J, D’herbomez M, Decoulx M, Wémeau JL, 2000 Resistance to thyroid hormone in a family with no TRbeta gene anomaly: pathogenic hypotheses. Ann Endocrinol (Paris) 61: 194–199.Google Scholar
- 18.Reutrakul S, Sadow PM, Pannain S, et al, 2000 Search for abnormalities of nuclear corepressors, coactivators, and a coregulator in families with resistance to thyroid hormone without mutations in thyroid hormone receptor beta or alpha genes. J Clin Endocrinol Metab 85: 3609–3617.PubMedGoogle Scholar
- 25.Yagi H, Pohlenz J, Hayashi Y, Sakurai A, Refetoff S, 1997 Resistance to thyroid hormone caused by two mutant thyroid hormone receptors beta, R243Q and R243W, with marked impairment of function that cannot be explained by altered in vitro 3,5,3′-triiodothyroinine binding affinity. J Clin Endocrinol Metab 82: 1608–1014.PubMedGoogle Scholar