Duoxa2-flox Mouse

DUOXA2, encoding dual oxidase maturation factor 2, is crucial for the maturation and activation of dual oxidase DUOX2, a member of the NADPH oxidase family. It enables DUOX2 to correctly migrate from the endoplasmic reticulum to the plasma membrane, and together they form a stable complex promoting hydrogen peroxide (H2O2) generation in thyroid hormone synthesis [2].

Mutations in DUOXA2 lead to defects in the function of the DUOX2 protein, causing inherited congenital hypothyroidism (CH). In a study of 377 CH cases, DUOXA2 was prominent in thyroid dysgenesis (TD) cases (18.75%) [1]. A case report described a girl with CH having a homozygous nonsense DUOXA2 mutation (p.Tyr138*), and her apparently unaffected brother also had the identical homozygous mutation, suggesting a broader phenotypic spectrum of DUOXA2 mutations [3]. In a cross-sectional study of borderline CH cases, 12% of patients harbored likely pathogenic mutations in DUOXA2, including novel gene variants [4]. In 21 Chinese Han patients with thyroid dyshormonogenesis, 3 rare non-polymorphic variants in DUOXA2 were found [5]. In a study of 110 Chinese patients with primary CH, autosomal recessive inheritance of CH caused by mutations in DUOXA2 was confirmed [6].

In conclusion, DUOXA2 is essential for the proper function of DUOX2 in thyroid hormone synthesis. Studies on DUOXA2 mutations in patients with CH, especially those with TD, have expanded our understanding of the role of DUOXA2 in CH pathogenesis, highlighting its significance in the genetic etiology of this common pediatric metabolic disorder.