Genetic and functional analysis of two missense mutations in congenital hypothyroidism and goiter.

Mutations in the dual oxidase 2 gene () impair hydrogen peroxide (HO) production and cause dyshormonogenesis. In addition, these mutations have been implicated in autosomal recessive congenital hypothyroidism (CH) with goiter. In this study, we identified mutations that were causative for CH and explored the effects of these mutations on DUOX2 function. Blood samples were collected from 10 infants born with CH and goiter to unrelated parents. We extracted genomic DNA and sequenced all exons by polymerase chain reaction direct sequencing. The effects of mutations were characterized by HO production assays and cycloheximide (CHX) chase experiments. Sequence analysis revealed one novel mutation and one known mutation in unrelated families: c.1060C>T (p.R354W) and c.3616 G>A (p.A1206T). Both mutations impaired HO production. CHX chase experiments demonstrated the mutants had shorter half-lives and degraded more rapidly than wild-type Our study identified two novel mutations in Chinese patients with CH and goiter, which were responsible for the deficit in the organification process.