USH2A

Several dozen mutations in the USH2A gene have been reported to cause retinitis pigmentosa, a vision disorder that causes the light-sensing cells of the retina to gradually deteriorate. 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 associated with other signs and symptoms as part of a genetic syndrome (such as Usher syndrome, described below).

The USH2A gene mutations that cause 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 called photoreceptors in the retina. A loss of these cells underlies the progressive vision loss characteristic of this condition.

More than 400 mutations in the USH2A gene have been identified in people with Usher syndrome type II, which is characterized by a combination of hearing loss and vision loss associated with retinitis pigmentosa. Specifically, USH2A gene mutations cause a form of the disorder known as Usher syndrome type IIA (USH2A), which accounts for more than half of all cases of Usher syndrome type II.

Several of these mutations change single 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.