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

Hormones (Athens). 2019 Jun;18(2):223-227. doi: 10.1007/s42000-019-00094-9. Epub 2019 Feb 12.


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.

Keywords: Hypothyroid; Resistance to thyroid hormone; Thyroid hormone receptor alpha.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Substitution
  • Child, Preschool
  • DNA Mutational Analysis
  • Follow-Up Studies
  • Humans
  • Male
  • Mutation, Missense*
  • Polymorphism, Single Nucleotide
  • Thyroid Function Tests
  • Thyroid Hormone Receptors alpha / genetics*
  • Thyroid Hormone Resistance Syndrome / diagnosis
  • Thyroid Hormone Resistance Syndrome / genetics*


  • Thyroid Hormone Receptors alpha