CDH23

The CDH23 gene provides instructions for making a protein called cadherin 23, a type of protein that helps cells stick together. Different cell types make different versions of this protein, including a short version in the light-sensitive layer in the back of the eye (the retina) and a longer version in the inner ear. Cadherin 23 interacts with other proteins in the cell membrane as part of a protein complex that is involved in cell attachment.

Research suggests that the cadherin 23 protein complex shapes inner ear structures called hair bundles. These structures are made of stereocilia, which are hairlike projections that bend in response to sound waves. This bending motion is critical for converting sound waves to nerve impulses, which is an essential process for normal hearing. The protein complex may organize hair bundles by cross-linking the stereocilia and helping to promote the transmission of sound waves.

In the retina, the role of the cadherin 23 protein complex is less well understood. Its presence in specialized cells that detect light and color (photoreceptor cells) suggests that it plays a critical role in the development and function of these cells.

nonsyndromic deafness - caused by mutations in the CDH23 gene

Approximately 20 mutations in the CDH23 gene have been identified in people with a type of nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body) called DFNB12. Most of these mutations change a single protein building block (amino acid) used to make cadherin 23. These mutations alter, but do not totally eliminate, the normal function of this protein. If cadherin 23 does not work properly, deafness results from disrupted development of stereocilia in the inner ear.

Researchers speculate that some children with nonsyndromic hearing loss caused by a CDH23 mutation may actually have an early form of Usher syndrome. A few children with CDH23-related deafness have gone on to develop retinitis pigmentosa, a vision disorder characteristic of Usher syndrome, later in life.

Usher syndrome - caused by mutations in the CDH23 gene

More than 30 mutations in the CDH23 gene have been shown to cause Usher syndrome type 1D. Many of these mutations change one DNA building block (base pair) in the CDH23 gene. Most genetic changes disrupt protein production, resulting in an abnormally small, nonfunctional version of cadherin 23. Insertions of small amounts of DNA in the CDH23 gene can also result in a nonfunctional version of this protein. A deficiency of cadherin 23 can lead to improper development of the inner ear and retina, resulting in the loss of hearing and vision typical of Usher syndrome.