USH2A

The USH2A gene provides the instructions for making a protein called usherin. Usherin is an important component of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. Usherin is found in the inner ear and the part of the eye that detects light and color (the retina). Although the function of usherin has not been well established, studies suggest that this protein is part of a larger protein complex that plays an important role in inner ear and retinal development. In these locations, the protein complex may also be involved in the function of synapses, which are junctions between nerve cells where cell-to-cell communication occurs.

Usher syndrome - caused by mutations in the USH2A gene

More than 200 mutations in the USH2A gene have been identified in people with Usher syndrome type IIA. Several of these mutations change single protein building blocks (amino acids) in the usherin protein. In some cases, these mutations lead to the production of an abnormally short version of the protein or prevent the cell from making any functional usherin. Other mutations insert or delete small amounts of DNA in the USH2A gene, which probably impairs the normal function of usherin. Researchers have not determined how a missing or altered usherin protein leads to the signs and symptoms of Usher syndrome.

The most common mutation in the USH2A gene is found in about 25 percent of people with Usher syndrome type IIA, particularly those from Europe, the United States, South Africa, and China. This mutation deletes a specific DNA building block, a guanine (G) nucleotide, at position 2299 in the USH2A gene (written as 2299delG). Individuals with this change, or with similar mutations in the USH2A gene, develop moderate to severe hearing loss and retinitis pigmentosa, a disorder that results in loss of vision.

other disorders - caused by mutations in the USH2A gene

At least four mutations in the USH2A gene have been reported to cause retinitis pigmentosa. This disorder affects the retina, resulting in vision loss that occurs as light-sensing cells in the retina gradually deteriorate.

The mutations responsible for retinitis pigmentosa change single protein building blocks (amino acids) in the usherin protein. Unlike patients with Usher syndrome type IIA, people with these mutations do not experience hearing loss. Approximately 25 percent to 50 percent of patients with retinitis pigmentosa have mutations in the USH2A gene.