DUOX2 Gene Mutation Manifesting as Resistance to Thyrotropin Phenotype

Resistance to thyrotropin (TSH) (RTSH; defined by elevated TSH and a normal or hypoplastic thyroid gland) can be caused by mutations in genes encoding the TSH receptor and PAX8 , and it has been linked to a locus on chromosome 15. In two nonconsanguineous families with nongoitrous euthyroid hyperthyrotropinemia, typical of the RTSH phenotype, exome analysis identified five rare DUOX2 gene variants (p.A649E, p.P1391A, p.R885L, p.G488R, and p.SF965-6SfsX29) found to be pathogenic. This form of nongoitrous dyshormonogenesis masquerades both clinically and biochemically as RTSH. Accordingly, mutations in DUOX2 should be added to those of SLC26A4 as causes of RTSH.