GUCY2D

The GUCY2D gene provides instructions for making a protein that plays an essential role in normal vision. This protein is found in the retina, which is the specialized tissue at the back of the eye that detects light and color. Within the retina, the GUCY2D protein is located in light-detecting cells called photoreceptors. The retina contains two types of photoreceptor cells: rods and cones. Rods are needed for vision in low light, while cones are needed for vision in bright light, including color vision.

The GUCY2D protein is involved in a process called phototransduction. When light enters the eye, it stimulates specialized pigments in photoreceptor cells. This stimulation triggers a series of chemical reactions that produce an electrical signal, which is interpreted by the brain as vision. Once photoreceptors have been stimulated by light, they must return to their resting (or "dark") state before they can be stimulated again. The GUCY2D protein is responsible for a chemical reaction that helps return photoreceptors to their dark state after light exposure.

Leber congenital amaurosis - caused by mutations in the GUCY2D gene

More than 50 mutations in the GUCY2D gene have been found to cause Leber congenital amaurosis. Mutations in this gene account for 6 to 21 percent of all cases of this condition.

The mutations responsible for Leber congenital amaurosis occur in both copies of the GUCY2D gene in each cell. Most of these genetic changes lead to an abnormally short, nonfunctional version of the GUCY2D protein. A lack of this protein prevents photoreceptor cells from returning to their dark state after they are exposed to light. As a result, the process of phototransduction is almost totally shut down, leading to severe visual impairment beginning very early in life.

other disorders - caused by mutations in the GUCY2D gene

At least six mutations in the GUCY2D gene have been identified in people with another vision disorder called cone-rod dystrophy. The vision problems associated with this condition include a loss of sharpness (reduced acuity), an increased sensitivity to light (photophobia), nearsightedness (myopia), and impaired color vision. These vision problems tend to worsen over time.

Most of the GUCY2D gene mutations responsible for cone-rod dystrophy affect a particular protein building block (amino acid) in the GUCY2D protein, replacing the amino acid arginine at position 838 with one of several other amino acids. A few mutations alter other amino acids in the same region of the protein.

The mutations that cause cone-rod dystrophy typically occur in one of the two copies of the GUCY2D gene in each cell. These genetic changes impair normal phototransduction, which causes the progressive vision problems found in cone-rod dystrophy.