High prevalence of DUOX2 mutations in Japanese patients with permanent congenital hypothyroidism or transient hypothyroidism

J Pediatr Endocrinol Metab. 2016 Jul 1;29(7):807-12. doi: 10.1515/jpem-2015-0400.


Background: Dual oxidase 2 (DUOX2) mutations are a cause of dyshormonogenesis (DH) and have been identified in patients with permanent congenital hypothyroidism (PH) and with transient hypothyroidism (TH). We aimed to elucidate the prevalence and phenotypical variations of DUOX2 mutations.

Methods: Forty-eight Japanese DH patients were enroled and analysed for sequence variants of DUOX2, DUOXA2, and TPO using polymerase chain reaction-amplified direct sequencing.

Results: Fourteen sequence variants of DUOX2, including 10 novel variants, were identified in 11 patients. DUOX2 variants were more prevalent (11/48, 22.9%) than TPO (3/48, 6.3%) (p=0.020). The prevalence of DUOX2 variants in TH was slightly, but not significantly, higher than in PH. Furthermore, one patient had digenic heterozygous sequence variants of both DUOX2 and TPO.

Conclusions: Our results suggest that DUOX2 mutations might be the most common cause of both PH and TH, and that phenotypes of these mutations might be milder than those of other causes.

MeSH terms

  • Amino Acid Substitution
  • Autoantigens / genetics
  • Cohort Studies
  • Congenital Hypothyroidism / epidemiology
  • Congenital Hypothyroidism / ethnology
  • Congenital Hypothyroidism / genetics*
  • Congenital Hypothyroidism / physiopathology
  • DNA Mutational Analysis
  • Dual Oxidases
  • Female
  • Gene Deletion
  • Hospitals, University
  • Humans
  • Hypothyroidism / epidemiology
  • Hypothyroidism / ethnology
  • Hypothyroidism / genetics*
  • Hypothyroidism / physiopathology
  • Infant, Newborn
  • Iodide Peroxidase / genetics
  • Iron-Binding Proteins / genetics
  • Japan / epidemiology
  • Male
  • Mutation*
  • Mutation, Missense
  • NADPH Oxidases / genetics*
  • Neonatal Screening
  • Prevalence
  • Referral and Consultation
  • Retrospective Studies
  • Severity of Illness Index
  • Thyroid Gland / physiopathology*


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