PAX6

The PAX6 gene belongs to a family of genes that play a critical role in the formation of tissues and organs during embryonic development. The members of the PAX gene family are 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 and help control the activity (expression) of particular genes. On the basis of this action, PAX proteins are called transcription factors.

During embryonic development, the PAX6 protein is thought to activate genes involved in the formation of the eyes, brain and spinal cord (central nervous system), and the pancreas. Within the brain, PAX6 is involved in the development of a specialized group of brain cells that process smell (the olfactory bulb). Researchers believe that the PAX6 protein controls many aspects of eye development. Following birth, the PAX6 protein is active in many structures of the eyes and likely regulates the expression of various genes.

aniridia - caused by mutations in the PAX6 gene

More than 250 mutations in the PAX6 gene have been found to cause aniridia, an absence of the colored part of the eye (the iris). Most of these mutations create a premature stop signal in the instructions for making the PAX6 protein. These mutations lead to the production of an abnormally short, nonfunctional PAX6 protein. As a result, there is less PAX6 protein to regulate the activity of other genes.

The majority of mutations that cause aniridia occur within the PAX6 gene; however, some disease-causing mutations occur in neighboring regions of DNA that normally regulate the expression of the PAX6 gene, known as regulatory regions. Mutations in PAX6 gene regulatory regions reduce the expression of the PAX6 gene. These mutations lead to a shortage of functional PAX6 protein, which disrupts the formation of the eyes during embryonic development.

Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome - associated with the PAX6 gene

The PAX6 gene is located in a region of chromosome 11 that is deleted in people with Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome, more commonly known by the acronym WAGR syndrome. As a result of this deletion, affected individuals are missing one copy of the PAX6 gene in each cell. A loss of the PAX6 gene is associated with the characteristic eye features of WAGR syndrome, including aniridia, and may affect brain development.

other disorders - associated with the PAX6 gene

Mutations in the PAX6 gene can cause eye problems other than aniridia. The mutations that cause these eye problems occur in one copy of the PAX6 gene in each cell. Most of these mutations change single protein building blocks (amino acids) in the PAX6 protein. These mutations reduce but do not eliminate the protein's function and are less severe than mutations that cause aniridia. Most of the mutations reduce the protein's ability to bind to DNA, disrupting its role as a transcription factor.

Individuals with a relatively mild mutation in the PAX6 gene may have one or more eye problems, which can cause severe visual impairment. People with one of these mutations may be born with pupils that are not centrally positioned in the eye (ectopia papillae), small eyes (microphthalmia), and underdeveloped optic nerves, structures that carry information from the eyes to the brain. Mild PAX6 mutations can also result in a gap or split in structures that make up the eye (coloboma) or an underdeveloped region at the back of the eye responsible for sharp central vision (the fovea). Additional conditions caused by these PAX6 gene mutations may be present at birth or develop later, such as a clouding of the lens of the eye (cataracts), involuntary eye movements (nystagmus), inflammation of the front surface of the eye called the cornea (keratitis), and thinning and clouding of the cornea (Peters anomaly).