USH2A

The USH2A gene provides 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 layer of light-sensitive tissue at the back of the eye (the retina). Although the function of usherin has not been well established, studies suggest that it is part of a group of proteins (a 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.

retinitis pigmentosa - caused by mutations in the USH2A gene

Several mutations in the USH2A gene have been reported to cause retinitis pigmentosa. USH2A gene mutations are the most common cause of the autosomal recessive form of retinitis pigmentosa, accounting for 10 to 15 percent of all cases. This form of the disorder is described as nonsyndromic, which means that it is not part of a larger genetic syndrome (such as Usher syndrome, described below).

The USH2A gene mutations that cause autosomal recessive retinitis pigmentosa change single protein building blocks (amino acids) in the usherin protein. Through a mechanism that is not well understood, these genetic changes lead to the gradual breakdown of specialized light receptor cells (photoreceptors) in the retina. A loss of these cells underlies the progressive vision loss characteristic of this condition.

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. These mutations often 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 hearing impairment and vision loss that are characteristic of Usher syndrome type IIA.

It is unclear why some USH2A gene mutations result in Usher syndrome type IIA, while other mutations cause retinitis pigmentosa without hearing loss.