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Disorders of H2O2 generation.

Marina Muzza1, Laura Fugazzola2

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|June 27, 2017
PubMed
Summary

Mutations in the thyroid hydrogen peroxide (H2O2) generation system DUOX2 are a leading cause of congenital hypothyroidism (CH) due to thyroid dyshormonogenesis, while DUOXA defects are rare. Phenotypic variability in CH is significant even within families.

Keywords:
DUOXDUOXAcongenital hypothyroidismdyshormonogenesis

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Area of Science:

  • Endocrinology
  • Genetics
  • Molecular Biology

Background:

  • Congenital hypothyroidism (CH) due to thyroid dyshormonogenesis can result from defects in the thyroid hydrogen peroxide (H2O2) generation system.
  • The dual oxidase (DUOX) enzyme and its maturation factor (DUOXA) are crucial for thyroid hormone synthesis.

Purpose of the Study:

  • To review the prevalence and impact of DUOX2 and DUOXA mutations in congenital hypothyroidism.
  • To explore genotype-phenotype correlations and explain the variability observed in DUOX2/A2 defects.

Main Methods:

  • Literature review of studies investigating DUOX2 and DUOXA mutations in CH patients.
  • Analysis of reported genotype-phenotype correlations and proposed mechanisms for variability.

Main Results:

  • DUOX2 mutations are a frequent cause of CH due to dyshormonogenesis, whereas DUOXA defects are rarely implicated.
  • Significant intra- and inter-familial phenotype variability is a consistent feature of DUOX2/A2 defects.

Conclusions:

  • DUOX2 defects are a primary genetic cause of CH, highlighting the importance of this pathway.
  • The observed phenotypic variability may be attributed to factors including other H2O2 systems, age-related hormone needs, ethnicity, iodine intake, and methodological differences.