CONSEQUENCES OF ELASTIN GENE MUTATIONS IN AUTOSOMAL DOMINANT CUTIS LAXA AND SUPRAVALVULAR AORTIC STENOSIS

Abstract

Extracellular matrix (ECM) and associated molecules have a myriad of roles comprising cell-cell communication, cell proliferation, migration, cell differentiation, development and survival. Elastic fibers are major insoluble components of ECM that are vital for connective tissues including large arteries, skin, lung, ligaments, and auricular cartilage. Their function is to provide elastic stretch and recoil to the conncevtive tissues. Elastin (ELN) is the key insoluble protein in the elastic fibers and it is the primary provider of elasticity and resilience. Structural abnormalities in elastin lead to a decrease in the integrity of elastic tissues including skin, lungs and large blood vessels. Therefore, elastin gene mutations lead to several skin, cardiovascular and pulmonary phenotypes including Williams Beuren syndrome, autosomal dominant cutis laxa (ADCL) and supravalvular aortic stenosis (SVAS). ADCL is characterized by loose and inelastic skin, pulmonary emphysema, aortic root dilation, and peripheral pulmonary aortic stenosis. SVAS is characterized by narrowing of the ascending aorta. While ADCL is caused by the frameshift mutations at the 3’ end of the ELN gene, missense and truncation mutations throughout the ELN gene lead to SVAS. In this review, we discussed and compared the latest information including clinical presentation, mutational spectrum and molecular mechanisms in ADCL and SVAS.