GJB6

The GJB6 gene provides instructions for making a protein called gap junction beta 6, more commonly known as connexin 30. Connexin 30 is a member of the connexin protein family. Connexin proteins form channels called gap junctions that permit the transport of nutrients, charged atoms (ions), and signaling molecules between neighboring cells. The size of the gap junction and the types of particles that move through it are determined by the particular connexin proteins that make up the channel. Gap junctions made with connexin 30 transport potassium ions and certain small molecules.

Connexin 30 is found in several different tissues throughout the body, including the brain, skin, and inner ear. Because of its presence in the inner ear, researchers are interested in this protein's role in hearing. Hearing requires the conversion of sound waves to electrical nerve impulses. This conversion involves many processes, including maintaining the proper level of potassium ions in the inner ear. Some studies indicate that gap junctions made with connexin 30 help to maintain the correct level of potassium ions. The GJB6 gene also plays a role in the growth and maturation of the outermost layer of skin (the epidermis).

nonsyndromic deafness - caused by mutations in the GJB6 gene

Researchers have identified a few GJB6 mutations in individuals with a form of nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body) called DFNB1. DFNB1 deafness is inherited in an autosomal recessive manner, which means that two copies of an altered gene in each cell are necessary to cause hearing loss. Some cases of DFNB1 deafness are caused by mutations that delete a large segment of DNA in both copies of the GJB6 gene. More commonly, however, a deletion occurs in one copy of the GJB6 gene, and a different mutation occurs in one copy of a neighboring gene called GJB2. Although the effect of a deletion in the GJB6 gene is unclear, it probably reduces the number of functional gap junctions. As a result, the proper level of potassium ions in the inner ear could be disturbed, disrupting the conversion of sound waves to nerve impulses.

One GJB6 mutation has been reported in individuals with a form of nonsyndromic deafness called DFNA3, which is inherited in an autosomal dominant manner. This type of inheritance means that one copy of an altered GJB6 gene in each cell is sufficient to cause hearing loss. The GJB6 mutation changes one of the protein building blocks (amino acids) used to make connexin 30. In this case, the amino acid threonine is replaced by the amino acid methionine at protein position 5 (written as Thr5Met). Although the effect of this replacement is not fully understood, it appears to inhibit the activity of gap junctions. As a result, the proper level of potassium ions in the inner ear could be disturbed, disrupting the conversion of sound waves to nerve impulses.

other disorders - caused by mutations in the GJB6 gene

Three GJB6 mutations have been identified in people with a skin disorder called hidrotic ectodermal dysplasia, which is also known as Clouston syndrome. Characteristics of hidrotic ectodermal dysplasia include thickened skin on the hands and feet, hair loss, and fingernail abnormalities. Hearing loss is also reported in some individuals with this syndrome. GJB6 mutations change one of the protein building blocks (amino acids) used to make connexin 30. One mutation replaces the amino acid glycine with the amino acid arginine at protein position 11 (written as Gly11Arg). In other mutations, the amino acid valine is replaced by the amino acid glutamic acid at position 37 (Val37Glu), and the amino acid alanine is replaced by valine at position 88 (Ala88Val). Although the effect of these mutations is not fully understood, they probably cause abnormal transport activity through the gap junctions.