GJB6

At least four GJB6 gene mutations have been identified in people with a skin disorder called Clouston syndrome, which is also known as hidrotic ectodermal dysplasia 2. Characteristics of Clouston syndrome include fingernail abnormalities, hair loss, and thickened skin on the palms of the hands and soles of the feet. The GJB6 gene mutations that cause Clouston syndrome change single protein building blocks (amino acids) in the connexin 30 protein. Although the effects of these mutations are not fully understood, they lead to abnormalities in the growth, division, and maturation of cells in the hair follicles, nails, and skin.

Researchers have identified a few GJB6 gene mutations in individuals with nonsyndromic hearing loss, which is loss of hearing that is not associated with other signs and symptoms. Mutations in this gene cause a form of nonsyndromic hearing loss called DFNA3. This form of hearing loss can either be present before a child learns to speak (prelingual) or begin after a child learns to speak (postlingual). The hearing loss ranges from mild to profound, becomes more severe over time, and particularly affects the ability to hear high-frequency sounds.

At least two GJB6 gene mutations have been reported to cause DFNA3. Each of these mutations changes a single amino acid in connexin 30. The mutations are described as "dominant negative" because they lead to an abnormal version of connexin 30 that appears to block the formation of functional gap junctions. A shortage of these channels may alter the level of potassium ions in the inner ear, which would disrupt the conversion of sound waves to nerve impulses.