GJA1

The GJA1 gene provides instructions for making a protein called connexin43, which is one of 21 connexin proteins in humans. Connexins play a role in cell-to-cell communication by forming channels, or gap junctions, between cells. Gap junctions allow for the transport of nutrients, charged particles (ions), and other small molecules that carry necessary communication signals between cells. Connexin43 is found in many human tissues such as the eyes, skin, bone, ears, heart, and brain.

oculodentodigital dysplasia - caused by mutations in the GJA1 gene

More than 45 mutations in the GJA1 gene have been found to cause oculodentodigital dysplasia. Most of these mutations change one protein building block (amino acid) in connexin 43. A different change in the GJA1 gene causes people to have oculodentodigital dysplasia with palmoplantar keratoderma. Palmoplantar keratoderma is a condition that causes skin on the palms and the soles of the feet to become thick, scaly, and calloused. This mutation deletes two DNA building blocks (nucleotides) to create a premature stop signal in the instructions for making connexin43. As a result, an abnormally short, nonfunctional protein is produced.

Channels formed with abnormal connexin 43 proteins are often permanently closed, preventing the transport of any molecules. Some mutations prevent connexin 43 proteins from traveling to the cell surface where they are needed to form channels. These disruptions in channel function impair communication between cells, which is thought to cause the eye, teeth, and finger abnormalities characteristic of oculodentodigital dysplasia.

other disorders - caused by mutations in the GJA1 gene

GJA1 gene mutations have been found to cause deafness in a small number of African-Americans. Further research is needed to determine how common GJA1 mutations are among African-Americans and people in other ethnic groups with deafness.