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A novel thyroid hormone receptor alpha gene mutation, clinic characteristics, and follow-up findings in a patient with thyroid hormone resistance

  • Ozlem KorkmazEmail author
  • Samim Ozen
  • Taha Resid Ozdemir
  • Damla Goksen
  • Sukran Darcan
Case Report


Thyroid hormone receptor alpha (THRA) gene mutation is a thyroid hormone resistance syndrome characterized by near-normal thyroid function tests and tissue-specific hypothyroidism. In this case study, we report a novel de novo p.G291S heterozygous mutation in the THRA gene was detected at mutation analysis. A 4-year-old male patient was admitted due to short stature, motor-mental retardation, and constipation. At physical examination, coarse facial appearance, eyelid edema, pallor, and umbilical hernia were observed. Primary thyroid hormone resistance should be considered in patients with phenotypically hypothyroid features. Laboratory analysis found moderate elevation in free triiodothyronine (T3) levels, normochromic normocytic anemia, and elevated creatine kinase levels. In conclusion, THRA gene mutation should be considered in patients with clinical hypothyroid findings and increased/moderately elevated free T3, decreased/ normal free thyroxine, normal thyroid-stimulating hormone levels, and increased muscle enzymes.


Resistance to thyroid hormone Thyroid hormone receptor alpha Hypothyroid 


Compliance with ethical standards

Conflict of interest

None declared.

Informed consent

Informed consent was obtained from the patients’ parents for publication.


None declared.

Employment or leadership

None declared.


  1. 1.
    Flamant F, Baxter JD, Forrest D et al (2006) International Union of Pharmacology. LIX. The pharmacology and classification of the nuclear receptor superfamily: thyroid hormone receptors. Pharmacol Rev 58:705–711CrossRefGoogle Scholar
  2. 2.
    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 85:3609–3617Google Scholar
  3. 3.
    Bochukova E, Schoenmakers N, Agostini M et al (2012) A mutation in the thyroid hormone receptor alpha gene. N Engl J Med 366:243–249CrossRefGoogle Scholar
  4. 4.
    Van Mullem A, Van Heerebeek R, Chrysis D et al (2012) Clinical phenotype and mutant TRalpha1. N Engl J Med 366:1451–1453CrossRefGoogle Scholar
  5. 5.
    Moran C, Chatterjee K (2016) Resistance to thyroid hormone alphaemerging defiition of a disorder of thyroid hormone action. J Clin Endocrinol Metab 101:2636–2639CrossRefGoogle Scholar
  6. 6.
    Moran C, Schoenmakers N, Agostini M et al (2013) An adult female with resistance to thyroid hormone mediated by defective thyroid hormone receptor alpha. J Clin Endocrinol Metab 98:4254–4261CrossRefGoogle Scholar
  7. 7.
    Moran C, Agostini M, Visser WE et al (2014) Resistance to thyroid hormone caused by a mutation in thyroid hormone receptor (TR)alpha1 and TRalpha2: clinical, biochemical, and genetic analyses of three related patients. Lancet Diab Endocrinol 2:619–626CrossRefGoogle Scholar
  8. 8.
    Van Mullem A, Chrysis D, Eythimiadou A et al (2013) Clinical phenotype of a new type of thyroid hormone resistance caused by a mutation of the TRalpha1 receptor: consequences of LT4 treatment. J Clin Endocrinol Metab 98:3029–3038CrossRefGoogle Scholar
  9. 9.
    Tylki-Szymanska A, Acuna-Hidalgo R, Krajewska-Walasek M et al (2015) Thyroid hormone resistance syndrome due to mutations in the thyroid hormone receptor alpha gene (THRA). J Med Genet 52:312–316CrossRefGoogle Scholar
  10. 10.
    Espiard S, Savagner F, Flamant F et al (2015) A novel mutation in THRA gene associated with an atypical phenotype of resistance to thyroid hormone. J Clin Endocrinol Metab 100:2841–2848CrossRefGoogle Scholar
  11. 11.
    Demir K, Van Gucht AL, Buyukinan M et al (2016) Diverse genotypes and phenotypes of three novel thyroid hormone receptor alpha mutations. J Clin Endocrinol Metab 101:2945–2954CrossRefGoogle Scholar
  12. 12.
    Van Gucht AL, Meima ME, Zwaveling-Soonawala N et al (2016) Resistance to thyroid hormone alpha in an 18-month-old girl: clinical, therapeutic, and molecular characteristics. Thyroid 26:338–346CrossRefGoogle Scholar
  13. 13.
    Richards S, Aziz N, Bale S et al (2015) ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405–424CrossRefGoogle Scholar
  14. 14.
    Vlaeminck-Guillem V, Espiard S, Flamant F, Wémeau JL (2015) TRa receptor mutations extend the spectrum of syndromes of reduced sensitivity to thyroid hormone. Presse Med 44:1103–1112CrossRefGoogle Scholar
  15. 15.
    Tang Y, Yu M, Lian X (2016) Resistance to thyroid hormone α, revelation of basic study to clinical consequences. J Pediatr Endocrinol Metab 29:511–522CrossRefGoogle Scholar
  16. 16.
    Van Gucht ALM, Meima ME, Moran C et al (2017) Anemia in patients with resistance to thyroid hormone α: a role for thyroid hormone receptor α in human erythropoiesis. J Clin Endocrinol Metab 102:3517–3525CrossRefGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2019

Authors and Affiliations

  1. 1.Ege University Faculty of Medicine Department of Pediatric Endocrinology and DiabetesEge UniversityIzmirTurkey
  2. 2.Tepecik Training and Research Hospital, Department of GeneticsHealth Sciences UniversityIzmirTurkey

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