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 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 mutations cause a form of the disorder called autosomal dominant cutis laxa, which is characterized by loose, sagging skin and an increased risk of an abnormal bulging (an aneurysm) in a large blood vessel called the aorta.

The ELN mutations that cause autosomal dominant cutis laxa lead to the production of an abnormally long version of the elastin protein. The abnormal protein likely interferes with 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.

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 aorta, which is the large artery that carries blood from the heart to the rest of the body. 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.