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Identification of four novel mutations in the thyroid hormone receptor-β gene in 164 Spanish and 2 Greek patients with resistance to thyroid hormone

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Abstract

OBJECTIVE

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.

DESIGN

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.

RESULTS

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.

CONCLUSIONS

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.

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Authors and Affiliations

  1. Endocrinology and Nutrition Department, Hospital Clínic i Universitari, Villarroel 170, 08036, Barcelona, Spain

    Antonio J. Amor & Irene Halperin

  2. Biochemistry and Molecular Genetics Department, Hospital Clínic i Universitari, Barcelona, Spain

    Josep Oriola

  3. Endocrinology and Nutrition Department, Hospital General Universitario, Alicante, Spain

    Rocío Alfayate, Montserrat Mauri & Antonio Picó

  4. Pediatrics Department, Hospital General de Granollers, Barcelona, Spain

    Victoria M. Borrás

  5. Pediatrics Department, Hospital Virgen de la Arrixaca, Murcia, Spain

    Arancha Escribano & Antonio Gutiérrez

  6. Endocrinology and Nutrition Department, Hospital Sant Pau, Barcelona, Spain

    Cintia González

  7. Pediatrics Department, Hospital Marina Baixa, Alicante, Spain

    Pilar Pérez

  8. Endocrinology and Metabolism Department, Venizelio General Hospital, Heraklio, Crete, Greece

    Irene Vourliotaki

Authors
  1. Antonio J. Amor
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  2. Irene Halperin
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  3. Rocío Alfayate
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  9. Pilar Pérez
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  10. Antonio Picó
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  11. Irene Vourliotaki
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  12. Josep Oriola
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Correspondence to Antonio J. Amor.

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Amor, A.J., Halperin, I., Alfayate, R. et al. Identification of four novel mutations in the thyroid hormone receptor-β gene in 164 Spanish and 2 Greek patients with resistance to thyroid hormone. Hormones 13, 74–78 (2014). https://doi.org/10.1007/BF03401322

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  • DOI: https://doi.org/10.1007/BF03401322

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