Study of DUOX2 and DUOXA2 Genes in Patients with Iodide Organification Defects

Presentation Number: MON-0391
Date of Presentation: June 23rd, 2014

Ester Saraiva Brust*, Cristine Barbosa Beltrao and Suemi Marui
Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil


The iodide organification is one of the main stages of thyroid hormonogenesis and requires adequate amounts of hydrogen peroxide, generated by DUOX/DUOXA system. DUOX2 and DUOXA2 are substantially expressed in thyroid tissue and have higher efficiency in the peroxide production. Patients with congenital hypothyroidism due to mutations in DUOXA2 and DUOX2 genes may present partial or total iodide organification defect.

Objective: Search for mutations in DUOX2 and DUOXA2 genes in patients with congenital hypothyroidism by partial and total iodide organification defects.

Methods: Seven patients were diagnosed with congenital hypothyroidism by iodide organification defect. All presented ectopic thyroid, elevated serum thyroglobulin, increased 131I uptake, positive perchlorate test and normal hearing. The coding region and exon/intron boundaries of DUOX2 and DUOXA2 genes (from peripheral leukocytes DNA) were amplified and automatically sequenced, and results were compared with normal sequences of each gene (GenBank).

Results: In DUOXA2 gene we identified 5 previously described polymorphisms. In DUOX2 gene we identified 20 polymorphisms already described in the literature and an unprecedented change. The new change in DUOX2 gene (p.A1087V) was identified in heterozygosity in one patient and also on his father (without thyroid disease, but not submitted to perchlorate test), 200 normal controls did not show the change. We have not identified any other changes in this patient. Among the polymorphisms identified in DUOX2 gene, p.H678R is described as functional, probably depending on the action of other changes present in DUOX2 or other proteins participants of hormonogenesis for its pathogenicity. The polymorphism was identified in 3 patients who also have important alterations in TPO gene, but their interaction could not be evaluated yet.

Conclusion: We have not identified mutations in the studied regions of DUOX2 and DUOXA2 genes. We identified previously described polymorphisms, including a functional polymorphism in DUOX2 gene. We also observed a change not described in DUOX2 gene (p.A1087V), only enzymatic studies may define the action of this change in the cause of congenital hypothyroidism in the patient.


Nothing to Disclose: ESB, CBB, SM