Identification and Functional Studies of Two New Dual-Oxidase 2 (DUOX2) Mutations in a Child with Congenital Hypothyroidism and a Eutopic Normal-Size Thyroid Gland

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 I-123 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. (J Clin Endocrinol Metab 94: 4309-4314, 2009)