RPGR

More than 300 mutations in the RPGR gene have been found to cause the X-linked form of retinitis pigmentosa. This condition primarily affects males, causing night blindness in early childhood followed by progressive daytime vision loss. RPGR gene mutations account for about 70 percent of all cases of X-linked retinitis pigmentosa.

Most of the mutations responsible for X-linked retinitis pigmentosa occur in the ORF15 exon of the RPGR protein. These mutations usually result in an abnormally short, malfunctioning protein. Changes in the structure of the RPGR protein likely disrupt the normal function of cilia in photoreceptor cells. However, it is unclear how these changes lead to the gradual loss of photoreceptors and resulting vision problems that are characteristic of retinitis pigmentosa.

Mutations in the RPGR gene can cause X-linked cone-rod dystrophy. The problems associated with this condition include a loss of visual sharpness (acuity), an increased sensitivity to light (photophobia), and impaired color vision. These vision problems worsen over time.

The genetic changes that cause X-linked cone-rod dystrophy likely disrupt the function of cilia in photoreceptor cells. It is unclear how these changes lead to the pattern of photoreceptor loss that results in cone-rod dystrophy.

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Although most RPGR gene mutations cause X-linked retinitis pigmentosa (described above), a few mutations in the ORF15 exon have been found in people with other retinal disorders. These include cone-rod dystrophy (described above), cone dystrophy, and atrophic macular degeneration. These retinal disorders are characterized by progressive vision abnormalities, although their signs and symptoms are distinct from retinitis pigmentosa.

Several additional RPGR gene mutations have been reported in people with a combination of retinitis pigmentosa and signs and symptoms affecting other parts of the body. In addition to progressive vision loss, affected individuals can have chronic respiratory and sinus infections, recurrent ear infections (otitis media), and hearing loss.

It is unclear why mutations in the RPGR gene can cause a variety of disorders. Studies suggest that certain mutations may disrupt the function of cilia in multiple tissues, including the inner ear and respiratory tract. Malfunctioning cilia in these tissues may underlie the hearing loss and respiratory abnormalities seen in some affected individuals. However, researchers are still working to determine how RPGR gene mutations cause specific abnormalities involving the retina and other parts of the body.