ESPN

The ESPN gene provides instructions for making a protein called espin. This protein is active in the inner ear, where it appears to play an essential role in normal hearing and balance. Researchers believe that espin binds to actin, a protein that is important for cell movement and shape. Espin is probably involved in the growth and maintenance of hairlike projections called stereocilia. Stereocilia, which are rich in actin, line the inner ear and bend in response to sound waves. This bending motion is essential for converting sound waves to nerve impulses and for conveying information about the body's position and movement.

Espin may also play a role in other types of sensory cells. Some studies suggest that this protein is present in taste receptor cells, cells involved in recognizing smells, and Merkel cells in the skin, which are associated with the sense of touch. In these cells, espin is located in small, fingerlike structures called microvilli that project from the cell surface. Like stereocilia in the inner ear, microvilli contain a large amount of actin.

nonsyndromic deafness - caused by mutations in the ESPN gene

At least six mutations in the ESPN gene have been identified in people with a form of nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body) called DFNB36. Several of these mutations cause an autosomal recessive form of nonsyndromic deafness that includes problems with balance. Autosomal recessive inheritance means that two copies of the gene in each cell are altered. These genetic changes delete a small amount of DNA from critical regions of the ESPN gene. Researchers believe that these genetic changes may prevent the production of espin or lead to an abnormally small, nonfunctional version of the protein that cannot bind to actin. A loss of espin function likely disrupts the development, structure, and organization of stereocilia, leading to hearing loss and balance problems.

Other ESPN mutations cause an autosomal dominant form of nonsyndromic hearing loss without obvious balance problems. Autosomal dominant inheritance means that one altered copy of the gene in each cell is sufficient to cause the condition. Most of these mutations alter a single protein building block (amino acid) in espin, which probably changes the structure of the protein. Although researchers have not determined how these mutations lead to hearing loss, they suspect that the altered protein disrupts the growth and organization of stereocilia in the inner ear.