ELN

The ELN gene provides instructions for making a protein called elastin. This protein is the major component of elastic fibers, which are slender bundles of proteins that provide strength and flexibility to connective tissues (tissues that support the body's joints and organs). Elastic fibers are found in the intricate lattice that forms in the spaces between cells (the extracellular matrix), where they give structural support to organs and tissues such as the heart, skin, lungs, ligaments, and blood vessels.

Williams syndrome - associated with the ELN gene

The ELN gene is located in a region of chromosome 7 that is deleted in people with Williams syndrome. As a result of this deletion, people with Williams syndrome are missing one copy of the ELN gene in each cell. This loss reduces the production of elastin by half, which disrupts the normal structure of elastic fibers in many connective tissues. Large blood vessels with abnormal elastic fibers are often thicker and less resilient than normal. These vessels can narrow, increasing the resistance to normal blood flow and leading to serious medical problems.

A loss of the ELN gene is associated with supravalvular aortic stenosis (SVAS), a form of cardiovascular disease that occurs frequently in people with Williams syndrome. Supravalvular aortic stenosis is a narrowing of the large blood vessel that carries blood from the heart to the rest of the body (the aorta). Other blood vessels can also be affected. If untreated, this condition can cause symptoms such as shortness of breath, chest pain, and ultimately heart failure.

Additionally, researchers believe that loss of the ELN gene is responsible for other connective tissue abnormalities, such as joint problems and loose skin, that are associated with Williams syndrome.

other disorders - caused by mutations in the ELN gene

Mutations in the ELN gene also cause supravalvular aortic stenosis in people without Williams syndrome. More than 40 mutations have been identified in the gene. Most of these genetic changes prevent one copy of the ELN gene in each cell from making any functional elastin protein. A reduction in the amount of elastin disrupts the normal structure of elastic fibers, which affects connective tissues such as the lining of large blood vessels. Abnormal thickening of the walls of the aorta underlies the serious complications associated with supravalvular aortic stenosis.

Other ELN mutations are responsible for a rare skin disorder called autosomal dominant cutis laxa. This disorder is characterized by skin that is loose, sagging, and inelastic. Cutis laxa can also affect connective tissue in other organs, including the heart, blood vessels, intestines, and lungs. Mutations in the ELN gene that cause cutis laxa lead to the production of an abnormally long version of the elastin protein. This abnormal protein likely interferes with the assembly of elastic fibers, which weakens connective tissue in the skin and other organs.