To date, the most common genetic cause of deafness is due to variants (mutations) in the gene that makes a protein called Connexin 26. People with Connexin 26-related deafness have what is known as sensorineural deafness (or "nerve deafness"), which means that a part of the ear, called the cochlea, cannot convert sound waves into a signal that can be sent to the brain. Two-thirds of people with Connexin 26-related deafness will have audiograms that fall into the profound-to-severe range, but there is quite a bit of variability in the range of hearing loss, including audiograms that fall into the mild and moderate range, and unilateral deafness, even among family members with the same genetic cause of deafness.

The gene that codes for Connexin 26 is called Gap Junction Beta 2 (GJB2). This gene is located on chromosome 13. The protein Connexin 26 is normally found in our outer skin cells and in the cochlea. Connexin 26 helps to create small channels (also known as gap junctions) between certain cells in the cochlea. These channels allow for the recycling of very small molecules, such as potassium, essential for hearing. People with Connexin 26-related deafness have a variant of the GJB2 gene that does not make the Connexin 26 protein. Therefore the channels do not form properly and potassium cannout be recycled in the cochlea.

There are more than 90 different known variants in the GJB2 gene that can cause deafness. Everyone has two copies of the GJB2 gene. In most cases, an individual will have Connexin 26-related deafness when both of their copies of GJB2 do not make the Connexin 26 protein. Genetic testing for the GJB2 gene looks at both copies of a person's GJB2 genes to try to find out if their GJB2 genes can make Connexin 26. This genetic testing may help explain the cause of deafness in some people.

In the last few years, scientists discovered another gene, called GJB6, which is found on chromosome 13 and makes a protein called Connexin 30. Like Connexin 26, Connexin 30 is normally found in the cochlea and is involved in recycling small molecules. In fact, Connexin 26 and Connexin 30 can work together in the cochlea. We now know that some people with Connexin 26-related deafness have a variant in the GJB2 gene and are missing a segment of the GJB6 gene; and for that reason it is important to test both genes, GJB2 and GJB6, to try to explain why a person is deaf and hard-of-hearing.

Our knowledge of Connexin 26-related deafness is still relatively new. Scientists are still identifying new variants in the GJB2 gene that may be related to deafness, and are constantly learning about this type of deafness. New information about Connexin 26-related deafness will likely become available in the coming years as more people have this test and more research is done in this area.

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