FBN1: The fibrillin 1 gene. This gene is mutated in Marfan syndrome, the MASS syndrome, and related disorders of connective tissue. The FBN1 gene produces a protein called fibrillin-1 which is transported out of the cell and deposited in the extracellular matrix, the intricate lattice in which cells are embedded to build tissues. In this matrix, fibrillin becomes part of small threadlike filaments called microfibrils, which in turn help build elastic fibers. Elastic fibers are essential for the function of flexible structures such as blood vessels, the lungs, and skin.
FBN1 is a very large gene, and more than 300 mutations in it have been identified that can cause Marfan syndrome. A mutation in the FBN1 gene alters the production of the fibrillin-1 protein or changes its structure. Patients with Marfan syndrome show decreased production of fibrillin-1, delayed transport of the protein out of the cell, or reduced amounts of the protein in the extracellular matrix. Ultimately, a mutation can lead to weakened structural support in key structures such as blood vessels, heart valves, cartilage, and ligaments.
Fibrillinopathies (type 1) are caused by defects in the fibrillin-1 protein, which is produced by the FBN1 gene. While Marfan syndrome is the most common type of fibrillinopathy, not all mutations in the FBN1 gene cause this syndrome. FBN1 mutations cause a spectrum of connective tissue disorders, with a broad range in severity and age of onset. Some FBN1 mutations cause a severe disorder that is fatal to newborns, while other mutations cause adult onset fibrillinopathies with a single abnormality, such as a dislocated lens in the eye or an abnormal aorta.