DOK7

The DOK7 gene provides instructions for making a protein that is necessary for the formation of connections between nerve cells and muscle cells, which occur in the neuromuscular junction. The neuromuscular junction is the area between the ends of nerve cells and muscle cells where signals are relayed to trigger muscle movement. The Dok-7 protein participates in turning on (activating) a protein called MuSK that plays a key role in organizing the various proteins important for the development and maintenance of the neuromuscular junction. In particular, the MuSK protein is involved in concentrating a protein called the acetylcholine receptor (AChR) in the muscle membrane at the neuromuscular junction." The AChR protein is critical for signaling between nerve and muscle cells, which is necessary for movement.

congenital myasthenic syndrome - caused by mutations in the DOK7 gene

At least 45 mutations in the DOK7 gene have been found to cause congenital myasthenic syndrome. A mutation that frequently occurs is the addition of four DNA building blocks (nucleotides) in the DOK7 gene (written as 1124_1127dupTGCC). Mutations in this gene lead to the production of a defective Dok-7 protein that cannot activate the MuSK protein. As a result, less AChR is present in the neuromuscular junction, which reduces signaling between nerve and muscle cells. These signaling abnormalities lead to decreased muscle movement and the muscle weakness characteristic of congenital myasthenic syndrome. For reasons that are unclear, people with mutations in the DOK7 gene tend to have muscle weakness in the shoulders, hips, and limbs, known as limb-girdle muscle weakness.