PAX6 gene

Aniridia

Genetic changes that cause disease are called pathogenic variants. Hundreds of pathogenic variants in the PAX6 gene have been found to cause aniridia. People with this condition have a partial or complete absence of the colored part of the eye (the iris) along with associated vision problems. Most of the pathogenic variants that cause aniridia create a premature stop signal in the instructions for making the PAX6 protein. This leads to the production of an abnormally short, nonfunctional protein. As a result, there are fewer PAX6 proteins to regulate the activity of other genes. Without enough functional PAX6 proteins, the formation of the eyes is disrupted before birth, leading to the various signs and symptoms of aniridia.

Coloboma

Pathogenic variants in the PAX6 gene can cause an eye problem called coloboma, in which there is a gap or split in one of the structures that make up the eye. Most of these variants lead to the substitution of one protein building block (amino acid) for another in the PAX6 protein. These variants reduce but do not eliminate the protein's ability to function. As a result, the PAX6 protein’s role as a transcription factor is impaired and eye formation during development is disrupted, leading to coloboma.

Peters anomaly

Pathogenic variants in the PAX6 gene have been found to cause Peters anomaly. This condition is characterized by the abnormal development of certain structures at the front of the eye and the clouding of the clear front surface of the eye (cornea). The variants that cause Peters anomaly lead to the substitution of one amino acid for another in the PAX6 protein. These changes reduce but do not eliminate the protein's ability to function. As a result, the PAX6 protein's ability to bind to DNA is reduced, disrupting its role as a transcription factor. This impairs the normal development of the eye, leading to the features of Peters anomaly. The same pathogenic variants in the PAX6 gene that cause Peters anomaly can also cause other, related eye disorders.

WAGR syndrome

The PAX6 gene is located in a region of chromosome 11 that is deleted in people with WAGR syndrome. WAGR syndrome is named for its main features: a childhood kidney cancer known as Wilms tumor, aniridia, genitourinary anomalies, and a range of developmental delays. As a result of this deletion, affected individuals are missing one copy of the PAX6 gene in each cell. The loss of the PAX6 gene is associated with the characteristic eye features of WAGR syndrome, including aniridia, and it may affect brain development.

Anophthalmia/Microphthalmia

MedlinePlus Genetics provides information about Anophthalmia/Microphthalmia

Other disorders

Pathogenic variants in the PAX6 gene can cause additional eye problems. Most of these variants lead to the substitution of one amino acid for another in the PAX6 protein. These variants reduce but do not eliminate the protein's ability to function, impairing its role as a transcription factor.

PAX6 gene variants often cause conditions that are apparent at birth, such as the pupils not being centrally positioned in the eye (ectopia pupillae) or the underdevelopment of the structures that carry information from the eyes to the brain (optic nerve hypoplasia). PAX6 gene variants can also lead to underdevelopment of a specific region at the back of the eye (fovea hypoplasia) that is responsible for clear vision.

Additional conditions caused by pathogenic variants in the PAX6 gene that may be present at birth or develop later include a clouding of the lenses of the eyes (cataracts), involuntary eye movements (nystagmus), and inflammation of the cornea (keratitis).

It is currently unclear why pathogenic variants in the PAX6 gene cause such a range of effects across the different areas of the eye.