PAX8

The PAX8 gene belongs to a family of genes that plays a critical role in the formation of tissues and organs during embryonic development. The PAX gene family is also important for maintaining the normal function of certain cells after birth. To carry out these roles, the PAX genes provide instructions for making proteins that attach to specific areas of DNA. By attaching to critical DNA regions, these proteins help control the activity of particular genes (gene expression). On the basis of this action, PAX proteins are called transcription factors.

During embryonic development, the PAX8 protein is thought to activate genes involved in the formation of the kidney and the thyroid gland. The thyroid gland is a butterfly-shaped tissue in the lower neck. It releases hormones that play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). Following birth, the PAX8 protein regulates several genes involved in the production of thyroid hormones.

congenital hypothyroidism - caused by mutations in the PAX8 gene

Several PAX8 gene mutations have been identified, but the effect of these mutations on health is variable. Some mutations cause congenital hypothyroidism, while others mildly reduce thyroid hormone levels or have no detectable effect. In some cases, identical mutations in members of the same family have varied effects.

Most mutations change one of the building blocks (amino acids) used to make the PAX8 protein. Other mutations disrupt protein production, resulting in an abnormally small version of the PAX8 protein. Nearly all PAX8 gene mutations prevent the PAX8 protein from effectively binding to DNA. One mutation alters interactions between the PAX8 protein and other transcription factors. As a result, the PAX8 protein cannot perform its role in regulating the activity of certain genes.

The thyroid gland is unusually small in people with PAX8 mutations. This finding suggests that PAX8 gene mutations disrupt the normal growth or survival of thyroid cells during embryonic development. As a result, the thyroid gland is reduced in size and may be unable to produce the normal amount of thyroid hormones.

tumors - associated with the PAX8 gene

The PAX8 gene is sometimes involved in the formation of thyroid tumors (neoplasms). In these cases, abnormal growth affects particular cells called follicular thyroid cells. Some of these growths, called follicular adenomas, are noncancerous (benign). Other tumors, known as follicular carcinomas, are cancerous (malignant). In some of these neoplasms, the PAX8 gene on chromosome 2 is fused with the PPARG gene on chromosome 3. The fusion results when segments of the two chromosomes are rearranged (translocated).

It remains unclear how the fused PAX8-PPARG gene affects the growth of follicular thyroid cells, or why some neoplasms become cancerous while others are benign. It is likely that the fused gene disrupts the normal control of cell division or triggers new cell activities that promote tumor formation.