ELN

The ELN gene provides instructions for making a protein called tropoelastin. Multiple copies of the tropoelastin protein attach to one another and are processed to form a mature protein called elastin. Elastin is the major component of elastic fibers, which are slender bundles of proteins that provide strength and flexibility to connective tissue (tissue that supports 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.

cutis laxa - caused by mutations in the ELN gene

Several mutations in the ELN gene have been identified in people with a skin disorder called cutis laxa. ELN gene mutations cause a form of the disorder called autosomal dominant cutis laxa, which is characterized by loose, sagging skin; an increased risk of an abnormal bulging (an aneurysm) in a large blood vessel called the aorta; and a lung disease called emphysema, which can make it difficult to breathe.

The ELN mutations that cause autosomal dominant cutis laxa lead to the production of an abnormally long version of the tropoelastin protein. The abnormal protein likely interferes with the formation of mature elastin and the assembly of elastic fibers, which weakens connective tissue in the skin and blood vessels. This defect in connective tissue underlies the major features of cutis laxa.

supravalvular aortic stenosis - caused by mutations in the ELN gene

At least 60 mutations in the ELN gene have been found to cause supravalvular aortic stenosis (SVAS), a heart defect present from birth that is characterized by a narrowing of the large blood vessel that carries blood from the heart to the rest of the body (the aorta). Most of the ELN gene mutations that cause SVAS lead to a decrease in the production of tropoelastin. A shortage of tropoelastin reduces the amount of mature elastin protein that is processed and available for forming elastic fibers. As a result, elastic fibers that make up the aorta are thinner than normal. To compensate, the smooth muscle cells that line the aorta increase in number, making the aorta thicker and narrower than usual. A thickened aorta is less flexible and resilient to the stress of constant blood flow and pumping of the heart. Over time, the wall of the aorta can become damaged. Aortic narrowing causes the heart to work harder to pump blood through the aorta, which can lead to shortness of breath, chest pain, and ultimately heart failure.

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.

In people with Williams syndrome, a loss of the ELN gene is associated with connective tissue abnormalities, such a joint problems and loose skin, and cardiovascular disease, particularly SVAS.