High prevalence of thyroid peroxidase gene mutations in patients with thyroid dyshormonogenesis

Eur J Endocrinol. 2007 May;156(5):511-9. doi: 10.1530/EJE-07-0037.


Objective: Thyroid dyshormonogenesis is a genetically heterogeneous group of inherited disorders in the enzymatic cascade of thyroid hormone synthesis that result in congenital hypothyroidism (CH). Thyroid peroxidase gene (TPO) mutations are one of the most common causes of thyroid dyshormonogenesis. The aim of this study was to identify TPO gene defects in a cohort of patients with thyroid dyshormonogenesis from Slovenia, Bosnia, and Slovakia.

Design and methods: Forty-three patients with permanent CH and orthoptic thyroid glands from 39 unrelated families participated in the study. Mutational analysis of the TPO gene and part of its promoter consisted of single-stranded conformation polymorphism analysis, sequencing, and restriction fragment length polymorphism (RFLP) analysis.

Results: TPO gene mutations were identified in 46% of participants. Seven different mutations were identified, four mutations of these being novel, namely 613C > T (R175X), 1519_1539del (A477_N483del), 2089G > A (G667S), and 2669G > A (G860R). Only a single allele mutation was identified in 65% of the TPO mutation carriers.

Conclusions: The results showed a higher prevalence of TPO gene mutations in thyroid dyshormonogenesis when compared with published studies. The high percentage of single allele mutations implied possible intronic or regulatory TPO gene mutations or monoallelic expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA / genetics
  • DNA Mutational Analysis / methods
  • Humans
  • Iodide Peroxidase / genetics*
  • Molecular Sequence Data
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single-Stranded Conformational
  • Promoter Regions, Genetic
  • Sequence Analysis, DNA
  • Thyroglobulin / blood
  • Thyroid Dysgenesis / blood
  • Thyroid Dysgenesis / enzymology*
  • Thyroid Dysgenesis / genetics*
  • Thyrotropin / blood
  • Thyroxine / blood


  • Thyrotropin
  • DNA
  • Thyroglobulin
  • Iodide Peroxidase
  • Thyroxine