CHX chase experiments demonstrated the <i>DUOX2</i> mutants had shorter half-lives and degraded more rapidly than wild-type <i>DUOX2.</i> Our study identified two novel <i>DUOX2</i> mutations in Chinese patients with CH and goiter, which were responsible for the deficit in the organification process.
After the identification of thyroid H<sub>2</sub>O<sub>2</sub> generation system (DUOX) and of its maturation factors (DUOXA), defects in DUOX2 and/or DUOXA2 were rapidly recognized as the possible cause of congenital hypothyroidism (CH) due to thyroid dyshormonogenesis.
This is a report of digenic mutations in DUOX1 and DUOX2 in association with CH, and we hypothesize that the inability of DUOX1 to compensate for DUOX2 deficiency in this kindred may underlie the severe CH phenotype.
Gene variants have been reported to be associated with congenital hypothyroidism (CH), the purpose of this study was to analyze the mutation spectrum and prevalence of 12 known causative genes (TSHR, PAX8, NKX2.1, NKX2.5, FOXE1, DUOX2, TG, TPO, GLIS3, NIS, SLC26A4 and DEHAL1) in CH in China.
The present study was aimed to investigate the prevalence, clinical, and molecular characteristics of congenital hypothyroidism (CH) caused by DUOX2 mutations in Guangzhou.
Sequencing other CH candidate genes in the patients with TPO variants revealed that patient 1 was homozygous for c.2422delT TPO mutation combined with double heterozygous DUOX2 pathogenic variants (p.R683L/p.L1343F) and patient 2 was triallelic for TPO pathogenic variants (p.R648Q/p.T561M/p.T561M).
Monoallelic TSHR pathogenic variants were associated with SCH, while TSHR pathogenic variants combined with monoallelic mutations in DUOX2 or TG gene might contribute to CH.
More recently, additional diseases have been linked to functionally altered variants in genes encoding for other NADPH oxidases, such as for DUOX2/DUOXA2 in congenital hypothyroidism, or for the Nox2 complex, NOX1 and DUOX2 as risk factors for inflammatory bowel disease.
These mice carry a spontaneous DUOX2 missense mutation, a T→G transversion, in exon 16 that changes the highly conserved valine 674 to glycine and results in severe congenital hypothyroidism.