<b>Objective:</b> We aimed to identify <i>DUOX1/DUOXA1</i> mutations and explore their role in the development of CH by investigating their functional impacts on H<sub>2</sub>O<sub>2</sub> generation.
Subsequent studies have revealed a homozygous DUOX1 mutation (c.1823-1G>C) resulting in aberrant splicing and a protein truncation (p.Val607Aspfs*43), which segregates with CH in this kindred.
Evidence of DUOX involvement in thyroidal H(2)O(2) production came from the identification of a DUOX2 nonsense homozygote mutation, which resulted in the absence of all functional domains of the protein, in a patient with permanent and severe congenital hypothyroidism (CH).
The identification of DUOXA genes has important implications for studies of the molecular mechanisms controlling DUOX expression and the molecular genetics of congenital hypothyroidism.