COL8A2 gene

At least two mutations in the COL8A2 gene have been found to cause a variant of Fuchs endothelial dystrophy, an eye disorder characterized by progressively blurry vision and sensitivity to bright light. COL8A2 gene mutations are associated with the rare, early-onset variant of Fuchs endothelial dystrophy, in which vision problems typically begin in a person's twenties.

The COL8A2 gene mutations that cause the early-onset variant of Fuchs endothelial dystrophy replace single protein building blocks in alpha 2(VIII) collagen. One mutation replaces the amino acid leucine with the amino acid tryptophan at position 450 (written as Leu450Trp or L450W). Another mutation replaces the amino acid glutamine with the amino acid lysine at position 455 (Gln455Lys or Q455K). These mutations impair the structure of alpha 2(VIII) collagen, probably preventing the abnormal protein from being incorporated into type VIII collagen fibers. As a result, there is a reduced amount of type VIII collagen in the cornea, specifically in Descemet's membrane. This abnormal Descemet's membrane leads to the death of the corneal endothelial cells, causing the cornea to become swollen with fluid. Corneal endothelial cells continue to die over time, which causes the vision problems in people with the early-onset variant of Fuchs endothelial dystrophy.