The FBLN5 gene provides instructions for making a protein called fibulin-5. This protein is part of a group of proteins called fibulins. Fibulins have a variety of functions in the extracellular matrix, which is the intricate lattice of proteins and other molecules that forms in the spaces between cells.
In the extracellular matrix, fibulin-5 appears to play a critical role in the assembly of elastic fibers. These slender bundles of proteins provide strength and flexibility to connective tissue (tissue that supports the body's joints and organs). Fibulin-5 is found in tissues and organs that are rich in elastic fibers, including developing arteries and the heart valves, lungs, and skin.
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At least four mutations in the FBLN5 gene have been identified in people with cutis laxa. Mutations in this gene can cause two different types of cutis laxa: an autosomal dominant form and an autosomal recessive form. In autosomal dominant cutis laxa, one copy of the altered FBLN5 gene in each cell is sufficient to cause the characteristic features of the disorder. In autosomal recessive cutis laxa, both copies of the gene in each cell must be altered to result in the disease.
The FBLN5 mutation known to cause autosomal dominant cutis laxa leads to the production of an abnormally long, nonfunctional version of fibulin-5. This abnormal protein interferes with the normal fibulin-5 produced from the other, unaltered copy of the FBLN5 gene. As a result, the amount of functional fibulin-5 in the extracellular matrix is severely reduced. A shortage of this protein prevents the assembly of elastic fibers, which weakens connective tissue in the skin, arteries, lungs, and other organs. These defects in connective tissue underlie the major features of cutis laxa.
Autosomal recessive cutis laxa results from FBLN5 mutations that change single protein building blocks (amino acids) in fibulin-5. These mutations alter the structure of the protein, trapping it within the cell. Because the defective fibulin-5 never makes it to the extracellular matrix, it is not available for the assembly of elastic fibers. A shortage of normal elastic fibers weakens connective tissue throughout the body, leading to the signs and symptoms of cutis laxa.
Researchers have been studying FBLN5 mutations as a possible risk factor for age-related macular degeneration, an eye disease that is a leading cause of vision loss among older people worldwide. Mutations in the FBLN5 gene have been found in a small number of people with age-related macular degeneration, but changes in this gene are probably not a major risk factor for this common eye disorder. A combination of genetic and environmental factors likely determine the risk of developing this disease.
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