PAX3

The PAX3 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. On the basis of this action, PAX proteins are called transcription factors.

During embryonic development, the PAX3 gene is active in cells called neural crest cells. These cells migrate from the developing spinal cord to specific regions in the embryo. The protein made by the PAX3 gene directs the activity of other genes (such as MITF) that signal neural crest cells to form specialized tissues or cell types such as limb muscles, bones in the face and skull (craniofacial bones), some nerve tissue, and pigment-producing cells called melanocytes. Melanocytes produce the pigment melanin, which contributes to hair, eye, and skin color. Melanocytes are also found in certain regions of the brain and inner ear.

Waardenburg syndrome - caused by mutations in the PAX3 gene

Several PAX3 mutations have been identified in people with Waardenburg syndrome, types I and III. Some of these mutations change one of the chemical building blocks (amino acids) used to make the PAX3 protein. Other mutations lead to an abnormally small version of the PAX3 protein. Researchers believe that all PAX3 mutations have the same effect; they destroy the ability of the PAX3 protein to bind to DNA and regulate the activity of other genes. As a result, melanocytes do not develop in certain areas of the skin, hair, eyes, and inner ear, leading to hearing loss and the patchy loss of pigmentation that are characteristic features of Waardenburg syndrome. Additionally, loss of PAX3 protein function disrupts development of craniofacial bones and certain muscles, producing the limb and facial features that are unique to Waardenburg syndrome, types I and III.

cancers - associated with the PAX3 gene

Alterations in the activity of the PAX3 gene are associated with some cases of cancer of muscle tissue (alveolar rhabdomyosarcoma) that occur mainly in adolescents and young adults. Gene activity is altered when the PAX3 gene on chromosome 2 is fused with the FOXO1A gene (also called FKHR) on chromosome 13. This fusion event occurs when segments of chromosomes 2 and 13 are rearranged in certain cells that develop into muscle tissue. The fused PAX3-FOXO1A gene may enhance changes that can lead to cancer, such as uncontrolled cell division and cell growth.

other disorders - caused by mutations in the PAX3 gene

One PAX3 mutation has been identified in individuals with a condition called craniofacial-deafness-hand syndrome. This condition is characterized by distinct facial features such as widely spaced eyes (hypertelorism) and a small nose, profound hearing loss, and hand abnormalities that affect the fingers and wrist. The mutation replaces the amino acid aspartic acid with the amino acid lysine at position 47 in the PAX3 protein (written as Asp47Lys). This mutation appears to affect the ability of the PAX3 protein to bind to DNA. As a result, the PAX3 protein does not function properly in neural crest cells, disrupting the development of craniofacial bones, the inner ear, and limb muscles.