OTOF

The OTOF gene provides instructions for making a protein called otoferlin. This protein is present in the brain and the cochlea, which is a snail-shaped structure in the inner ear that helps process sound. Although the exact function of otoferlin is uncertain, it appears to be essential for normal hearing. Researchers believe that otoferlin may play a role in releasing chemical signals (neurotransmitters) from nerve cells that are involved in hearing. This process is dependent on the concentration of calcium within the cell. The otoferlin protein has several regions called C2 domains that bind to calcium and use it to interact with other molecules.

nonsyndromic deafness - caused by mutations in the OTOF gene

At least 16 mutations in the OTOF 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 DFNB9. People with these mutations have a type of hearing loss called auditory neuropathy, which occurs when sound is not transmitted properly from the inner ear to the brain.

Some mutations in the OTOF gene result in the production of an abnormally small, nonfunctional version of otoferlin or prevent cells from making any of this protein. Other genetic changes probably alter the 3-dimensional structure of otoferlin, which impairs its ability to bind to calcium.

A particular OTOF mutation is a common cause of nonsyndromic deafness in the Spanish population. This mutation replaces one amino acid building block, glutamine, with a signal that stops protein production prematurely at position 829 in the otoferlin protein (written as Gln829Ter or Q829X). The Q829X mutation causes an abnormally short version of otoferlin to be made, which disrupts the protein's function and leads to hearing loss.