Ocular albinism is a genetic condition that primarily affects the eyes. This condition reduces the coloring (pigmentation) of the iris, which is the colored part of the eye, and the retina, which is the light-sensitive tissue at the back of the eye. Pigmentation in the eye is essential for normal vision.

Ocular albinism is characterized by severely impaired sharpness of vision (visual acuity) and problems with combining vision from both eyes to perceive depth (stereoscopic vision). Although the vision loss is permanent, it does not worsen over time. Other eye abnormalities associated with this condition include rapid, involuntary eye movements (nystagmus); eyes that do not look in the same direction (strabismus); and increased sensitivity to light (photophobia). Many affected individuals also have abnormalities involving the optic nerves, which carry visual information from the eye to the brain.

Unlike some other forms of albinism, ocular albinism does not significantly affect the color of the skin and hair. People with this condition may have a somewhat lighter complexion than other members of their family, but these differences are usually minor.

The most common form of ocular albinism is known as the Nettleship-Falls type or type 1. Other forms of ocular albinism are much rarer and may be associated with additional signs and symptoms, such as hearing loss.

Ocular albinism type 1 results from mutations in the GPR143 gene. This gene provides instructions for making a protein that plays a role in pigmentation of the eyes and skin. It helps control the growth of melanosomes, which are cellular structures that produce and store a pigment called melanin. Melanin is the substance that gives skin, hair, and eyes their color. In the retina, this pigment also plays a role in normal vision.

Most mutations in the GPR143 gene alter the size or shape of the GPR143 protein. Many of these genetic changes prevent the protein from reaching melanosomes to control their growth. In other cases, the protein reaches melanosomes normally but mutations disrupt the protein's function. As a result of these changes, melanosomes in skin cells and the retina can grow abnormally large. Researchers are uncertain how these giant melanosomes are related to vision loss and other eye abnormalities in people with ocular albinism.

Rare cases of ocular albinism are not caused by mutations in the GPR143 gene. In these cases, the genetic cause of the condition is often unknown.

Normal Function

The GPR143 gene, also known as OA1, provides instructions for making a protein that is involved in the coloring (pigmentation) of the eyes and skin. This protein is made in the light-sensitive tissue at the back of the eye (the retina) and in skin cells. The GPR143 protein is part of a signaling pathway that controls the growth and maturation of melanosomes, which are cellular structures that produce and store a pigment called melanin. Melanin is the substance that gives skin, hair, and eyes their color. In the retina, this pigment also plays a critical role in normal vision.

Health Conditions Related to Genetic Changes

Ocular albinism

More than 60 GPR143 mutations have been identified in people with the most common form of ocular albinism, which is called the Nettleship-Falls type or type 1. Most mutations alter the size or shape of the GPR143 protein. These genetic changes often prevent the abnormal protein from ever reaching melanosomes, where it is needed to control the growth of these pigment-containing structures. In other cases, the GPR143 protein reaches melanosomes normally but mutations prevent the protein from interacting with other molecules in its signaling pathway. Without functional GPR143 protein, melanosomes in skin cells and the retina can grow abnormally large. It is unclear how these giant melanosomes (macromelanosomes) are related to vision loss and other eye abnormalities in people with ocular albinism.

Most forms of albinism result from a reduced amount of melanin pigment within cells. Researchers continue to study why ocular albinism occurs when cells in the retina appear to contain a substantial amount of melanin. It is possible that this pigment is concentrated into a few abnormal macromelanosomes instead of being evenly distributed among many normal-sized melanosomes within the cell. Additional studies may help clarify the relationship between melanosomes, melanin distribution, and the reduced levels of pigmentation that are characteristic of ocular albinism.

Other Names for This Gene

• GP143_HUMAN
• OA1
• ocular albinism 1 (Nettleship-Falls)
• ocular albinism type 1 protein

Genomic Location

Ocular albinism type 1 is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the GPR143 gene in each cell is sufficient to cause the characteristic features of ocular albinism. Because females have two copies of the X chromosome, women with only one copy of a GPR143 mutation in each cell usually do not experience vision loss or other significant eye abnormalities. They may have mild changes in retinal pigmentation that can be detected during an eye examination.

The most common form of this disorder, ocular albinism type 1, affects at least 1 in 60,000 males. The classic signs and symptoms of this condition are much less common in females.