In vitro study of new DUOX2 mutants

Context: Some cases of congenital hypothyroidism (CH) are associated with a gland of normal size. Objective: To explore the cause of organification defect in one child with CH and a eutopic thyroid gland, genetic analyses of TPO, DUOX2, and DUOXA2 genes were performed. Patient: One child with CH, a eutopic thyroid gland, and a partial organification defect was shown after 123I scintigraphy and perchlorate test. Methods: In the child with the organification defect, TPO, DUOX2, and DUOXA2 genes were analyzed. The functional activity of the DUOX2 mutants was studied after expression in eukaryotic cells. Results: No TPO or DUOXA2 gene mutations were identified. Direct sequencing of the DUOX2 gene revealed a compound heterozygous genotype for S911L and C1052Y substitutions. S911L and C1052Y caused a partial defect in H2O2 production after transient expression in HeLa cells. Conclusions: We performed a genetic analysis in one child with CH and a eutopic thyroid gland. Two new mutations in DUOX2 gene responsible for the partial deficit in the organification process were identified. A new case of congenital hypothyroidism with a normally located thyroid gland and two new mutations in DUOX2 protein partially impairing H2O2 generation is described.