Mutational screening of the TPO and DUOX2 genes in Argentinian children with congenital hypothyroidism due to thyroid dyshormonogenesis

Endocrine. 2022 Jun;77(1):86-101. doi: 10.1007/s12020-022-03054-3. Epub 2022 May 4.


Purpose: Primary congenital hypothyroidism (CH) is the most common endocrine disease in children and one of the preventable causes of both cognitive and motor deficits. We present a genetic and bioinformatics investigation of rational clinical design in 17 Argentine patients suspected of CH due to thyroid dyshormonogenesis (TDH).

Methods: Next-Generation Sequencing approach was used to identify variants in Thyroid Peroxidase (TPO) and Dual Oxidase 2 (DUOX2) genes. A custom panel targeting 7 genes associated with TDH [(TPO), Iodothyrosine Deiodinase I (IYD), Solute Carrier Family 26 Member 4 (SLC26A4), Thyroglobulin (TG), DUOX2, Dual Oxidase Maturation Factor 2 (DUOXA2), Solute Carrier Family 5 Member 5 (SLC5A5)] and 4 associated with thyroid dysembryogenesis [PAX8, FOXE1, NKX2-1, Thyroid Stimulating Hormone Receptor (TSHR)] has been designed. Additionally, bioinformatic analysis and structural modeling were carried out to predict the disease-causing potential variants.

Results: Four novel variants have been identified, two in TPO: c.2749-2 A > C and c.2752_2753delAG, [p.Ser918Cysfs*62] and two variants in DUOX2 gene: c.425 C > G [p.Pro142Arg] and c.2695delC [p.Gln899Serfs*21]. Eighteen identified TPO, DUOX2 and IYD variants were previously described. We identified potentially pahogenic biallelic variants in TPO and DUOX2 in 7 and 2 patients, respectively. We also detected a potentially pathogenic monoallelic variant in TPO and DUOX2 in 7 and 1 patients respectively.

Conclusions: 22 variants have been identified associated with TDH. All described novel mutations occur in domains important for protein structure and function, predicting the TDH phenotype.

Keywords: Congenital Hypothyroidism; DUOX2; Gene; Mutation; Thyroid Dyshormonogenesis; Thyroid Peroxidase.

MeSH terms

  • Argentina
  • Autoantigens* / genetics
  • Child
  • Congenital Hypothyroidism* / genetics
  • Dual Oxidases* / genetics
  • Humans
  • Iodide Peroxidase* / genetics
  • Iron-Binding Proteins* / genetics
  • Mutation
  • Receptors, Thyrotropin / genetics


  • Autoantigens
  • Iron-Binding Proteins
  • Receptors, Thyrotropin
  • Dual Oxidases
  • TPO protein, human
  • Iodide Peroxidase
  • DUOX2 protein, human