NADPH Oxidases pp 667-693 | Cite as

DUOX Defects and Their Roles in Congenital Hypothyroidism

  • Xavier De DekenEmail author
  • Françoise Miot
Part of the Methods in Molecular Biology book series (MIMB, volume 1982)


Extracellular hydrogen peroxide is required for thyroperoxidase-mediated thyroid hormone synthesis in the follicular lumen of the thyroid gland. Among the NADPH oxidases, dual oxidases, DUOX1 and DUOX2, constitute a distinct subfamily initially identified as thyroid oxidases, based on their level of expression in the thyroid. Despite their high sequence similarity, the two isoforms present distinct regulations, tissue expression, and catalytic functions. Inactivating mutations in many of the genes involved in thyroid hormone synthesis cause thyroid dyshormonogenesis associated with iodide organification defect. This chapter provides an overview of the genetic alterations in DUOX2 and its maturation factor, DUOXA2, causing inherited severe hypothyroidism that clearly demonstrate the physiological implication of this oxidase in thyroid hormonogenesis. Mutations in the DUOX2 gene have been described in permanent but also in transient forms of congenital hypothyroidism. Moreover, accumulating evidence demonstrates that the high phenotypic variability associated with altered DUOX2 function is not directly related to the number of inactivated DUOX2 alleles, suggesting the existence of other pathophysiological factors. The presence of two DUOX isoforms and their corresponding maturation factors in the same organ could certainly constitute an efficient redundant mechanism to maintain sufficient H2O2 supply for iodide organification. Many of the reported DUOX2 missense variants have not been functionally characterized, their clinical impact in the observed phenotype remaining unresolved, especially in mild transient congenital hypothyroidism. DUOX2 function should be carefully evaluated using an in vitro assay wherein (1) DUOXA2 is co-expressed, (2) H2O2 production is activated, (3) and DUOX2 membrane expression is precisely analyzed.

Key words

NADPH oxidase Thyroid Congenital hypothyroidism DUOX DUOXA H2O2 Dual oxidase DUOX maturation factor Inherited disease 



The authors acknowledge the support of the “Fonds de la Recherche Scientifique” (FRS-FNRS), the “Fonds Docteur J.P. Naets” managed by the “Fondation Roi Baudouin,” and the “Fondation Tournay-Solvay.”


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Faculté de Médecine, Université Libre de Bruxelles (ULB)Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM)BrusselsBelgium

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