GUCY2D

Some variants (also known as mutations) in the GUCY2D gene have been identified in people with a vision disorder called cone-rod dystrophy. The problems associated with this condition include a loss of visual sharpness (acuity), an increased sensitivity to light (photophobia), and impaired color vision. These vision problems worsen over time.

The variants that cause cone-rod dystrophy occur in one of the two copies of the GUCY2D gene in each cell. These variants are responsible for about one-quarter of the cases of a form of the condition called autosomal dominant cone-rod dystrophy. Most of these variants 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. These genetic changes impair normal phototransduction, causing the photoreceptor cells to deteriorate over time. The loss of these cells leads to the progressive vision problems characteristic of cone-rod dystrophy.

Many variants  in the GUCY2D gene have been found to cause Leber congenital amaurosis. This condition is an eye disorder that primarily affects the retina. People with this disorder typically have severe visual impairment beginning at birth or shortly afterward. Variants in this gene account for 6 to 21 percent of all cases of this condition.

The variants that cause 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 in Leber congenital amaurosis.