Medical Definition of GJB2
GJB2: A gene that provides instructions to make a protein called gap junction beta 2. Mutations in the GJB2 gene are responsible for autosomal dominant and autosomal recessive forms of nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body) as well as some other genetic disorders.
The GJB2 gene is a member of the gap junction or connexin family. This family of genes produces protein subunits for channels (gap junctions) that connect neighboring cells. The channels (which are made from several protein subunits) permit the movement of nutrients, charged atoms (ions), and communication signals between cells. The size of the channel opening and the specific particles that move through the channel are determined by the protein subunits that make up the channel. For example, channels made with gap junction beta 2 protein permit the movement of potassium ions, along with other molecules.
Gap junction beta 2 protein is found in cells throughout the body, particularly in the inner ear and the skin. Because of its presence in the inner ear, especially the snail-shaped structure called the cochlea, researchers have focused on the role of this protein 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 channels made with gap junction beta 2 protein help to maintain the correct level of potassium ions. Other research suggests that the GJB2 gene is required for the maturation of certain cells in the cochlea. The GJB2 gene also plays a role in the growth and maturation of the outermost layer of skin (epidermis). Mutations in the GJB2 gene cause a number of diseases, including:
- Autosomal dominant nonsyndromic deafness -- Several GJB2 mutations have been identified that can cause nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body) inherited in an autosomal dominant manner. This type of inheritance means that one copy of an altered GJB2 gene is sufficient to cause hearing loss. The altered gene instructs the incorrect replacement of a single amino acid (the building material of proteins) in the gap junction beta 2 protein. The effect of these dominant mutations remains unclear. The altered protein probably inhibits the assembly of transport channels or their normal function, which could disrupt the conversion of sound waves to nerve impulses.
- Autosomal recessive nonsyndromic deafness -- More than 90 GJB2 mutations have been identified that can cause nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body) inherited in an autosomal recessive manner. This type of inheritance means that two copies of an altered GJB2 gene are necessary to cause hearing loss. These recessive mutations probably alter the transport channels between cells, disrupting proper levels of potassium ions. Levels of potassium ions that are too high may affect the function and survival of cells that are needed for hearing.
Some recessive mutations delete or insert base pairs, the building material of DNA. The most common mutation, particularly in the Caucasian (white) population, deletes 1 base pair between positions 30 and 35 in the gene sequence. This mutation is written as 30delG or 35delG. The deletion results in the production of an extremely short protein, which cannot form proper transport channels. Other deletions are frequently reported in Asian populations (235delC) and among people with an eastern European (Ashkenazi) Jewish ancestry (167delT).
GJB2 mutations can also cause an incorrect replacement of an amino acid (the building material of proteins) in the gap junction beta 2 protein. Substitution mutations can have various effects, including production of an unstable protein that is rapidly broken down, reduced assembly of transport channels, or formation of channels that do not function properly.
- Vohwinkel syndrome -- GJB2 mutations have been identified in this condition which is characterized by hearing loss and thickened skin, particularly on the knuckles, is caused by the replacement of aspartic acid with histidine at position 66 in the protein's chain of amino acids. This mutation is also written as Asp66His.
- Palmoplantar keratoderma with deafness -- Two GJB2 mutations have been reported in individuals with this condition in which the skin on the palms and soles of the feet is unusually thick. Glycine is replaced by alanine at position 59 (Gly59Ala), or arginine is replaced by glutamine at position 75 (Arg75Gln).
- Keratitis-ichthyosis-deafness (KID) syndrome -- Three GJB2 mutations that cause the keratitis-ichthyosis-deafness syndrome (the KID syndrome) have been identified. This syndrome is characterized by fishlike scaling of the skin, inflammation of the front surface of the eye (cornea), and deafness. The mutations involve one of the following amino acid substitutions: glycine replaced by arginine at position 12 (Gly12Arg), serine replaced by phenylalanine at position 17 (Ser17Phe), or aspartic acid replaced by tyrosine at position 50 (Asp50Tyr).
Gap junction beta 2 (GJB2) is also known as connexin 26.
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