PCDH15

The PCDH15 gene provides instructions for making a protein called protocadherin 15, a type of protein that helps cells stick together. Protocadherin 15 is made in the inner ear and in specialized cells in the eye that detect light and color (retinal photoreceptors), as well as in other tissues. This protein interacts with other proteins in the cell membrane to carry out its normal role in cell attachment.

In the inner ear, protocadherin 15 probably plays a role in the development and maintenance of hairlike projections called stereocilia. Stereocilia line the inner ear and 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 exact function of protocadherin 15 in the retina has not been determined, but it probably plays a role in the development and maintenance of specialized photoreceptor cells that detect light and color.

nonsyndromic deafness - caused by mutations in the PCDH15 gene

Researchers have identified a few mutations in the PCDH15 gene that cause a form of nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body) called DFNB23. These mutations lead to changes in single protein building blocks (amino acids) in the protocadherin 15 protein, which alter its normal structure and function. Deafness most likely results from the improper development of stereocilia in the inner ear.

Usher syndrome - caused by mutations in the PCDH15 gene

At least nine mutations that cause Usher syndrome type 1F have been identified in the PCDH15 gene. These mutations result in the production of an abnormally structured or shortened protein that may have little or no function in cells. In the Ashkenazi (eastern and central European) Jewish population, a common mutation replaces the amino acid arginine with a stop signal at position 245 (written as Arg245Ter or R245X) in the protocadherin 15 protein. As a result, an abnormally small version of the protein is made. This mutation may be the most common cause of Usher syndrome type 1 in this population. Because mutations in protocadherin 15 cause defects in the inner ear and retina, loss of hearing and vision can result.