CAV3

The CAV3 gene provides instructions for making a protein called caveolin-3, which is found in the membrane surrounding muscle cells. This protein is the main component of caveolae, small pouches in the muscle cell membrane. Within the caveolae, the caveolin-3 protein acts as a scaffold to organize other molecules that are important for cell signaling and maintenance of the cell structure.

limb-girdle muscular dystrophy - caused by mutations in the CAV3 gene

More than 20 mutations in the CAV3 gene have been identified in people with limb-girdle muscular dystrophy type 1C. Limb-girdle muscular dystrophy is a group of related disorders characterized by muscle weakness and wasting, particularly in the shoulders, hips, and limbs.

CAV3 gene mutations result in a shortage of caveolin-3 protein in the muscle cell membrane and a reduction in the number of caveolae. Researchers suggest that a shortage of caveolae impairs the structural integrity of muscle cells, interferes with cell signaling, and causes the self-destruction of cells (apoptosis). The resulting degeneration of muscle tissue leads to the signs and symptoms of limb-girdle muscular dystrophy.

other disorders - caused by mutations in the CAV3 gene

In addition to limb-girdle muscular dystrophy, CAV3 gene mutations cause four other conditions affecting muscles: isolated hyperCKemia, rippling muscle disease, distal myopathy, and hypertrophic cardiomyopathy. Collectively, the five conditions are called caveolinopathies when caused by mutations in the CAV3 gene.

In isolated hyperCKemia, affected individuals have elevated blood levels of an enzyme called creatine kinase. While elevated creatine kinase often accompanies muscle disease, individuals with isolated hyperCKemia have no muscle weakness or other symptoms.

Rippling muscle disease is a condition in which the muscles appear to be unusually sensitive to stimuli (irritable). Affected individuals may experience muscle cramps, stiffness, and muscles that appear to ripple when they move. Rippling muscles may also occur as a feature of limb-girdle muscular dystrophy type 1C.

Distal myopathy is a disorder in which weakness and loss of function mainly affect the muscles farthest from the main part of the body (distal muscles), such as those of the hands and feet.

Hypertrophic cardiomyopathy is a thickening of the cardiac muscle that forces the heart to work harder to pump blood. This condition is often associated with an abnormal heartbeat (arrhythmia) and can lead to heart failure and sudden death.

Any of the five caveolinopathies may be caused by a particular CAV3 gene mutation. It is unclear why a particular CAV3 gene mutation may cause different patterns of signs and symptoms, even within the same family.

Mutations in the CAV3 gene have also been identified in people with long QT syndrome, which is a heart condition that causes the heart (cardiac) muscle to take longer than usual to recharge between beats. The irregular heartbeats can lead to fainting (syncope) or cardiac arrest and sudden death. Researchers suggest that CAV3 gene mutations may affect the function of sodium channels located in the caveolae. These channels, which transport positively charged sodium atoms (sodium ions) into cells, play a key role in a cell's ability to generate and transmit electrical signals. In cardiac muscle, ion channels play critical roles in maintaining the heart's normal rhythm. A disruption in ion transport may alter the way the heart beats, leading to the abnormal heart rhythm characteristic of long QT syndrome. Long QT syndrome is not associated with skeletal muscle weakness.