DUOX2

The DUOX2 gene provides instructions for making an enzyme called dual oxidase 2. This enzyme is found in the thyroid gland (a butterfly-shaped tissue in the lower neck), salivary glands, the digestive tract, and airways in the throat and lungs. Dual oxidase 2 helps generate a chemical called hydrogen peroxide. In the thyroid, hydrogen peroxide is required for one of the final steps in the production of thyroid hormones. Thyroid hormones play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism).

congenital hypothyroidism - caused by mutations in the DUOX2 gene

Researchers have identified several DUOX2 mutations that cause congenital hypothyroidism. Most of these mutations result in an abnormally small version of the dual oxidase 2 enzyme. The remaining mutations change one of the building blocks (amino acids) used to make the enzyme, which probably alters the enzyme's structure. All DUOX2 mutations limit the enzyme's ability to generate hydrogen peroxide. Without sufficient hydrogen peroxide, thyroid hormone production is disrupted. In some cases, the thyroid gland is enlarged (goiter) in an attempt to compensate for reduced thyroid hormone production.

The reduction in thyroid hormone production is affected by the number of DUOX2 genes with a mutation. Each cell in the body has two copies of the DUOX2 gene. If both copies of the gene have a mutation, cells in the thyroid gland generate very little hydrogen peroxide. As a result, thyroid hormone levels are extremely low, causing severe congenital hypothyroidism. If only one copy of the DUOX2 gene is mutated, some hydrogen peroxide is produced. As a result, thyroid hormone levels are slightly reduced, causing mild congenital hypothyroidism. Sometimes, mild hypothyroidism is temporary (transient), and thyroid hormone levels that are low during infancy increase with age.