Molecular genetics of color-vision deficiencies

The normal X-chromosome-linked color-vision gene array is composed of a single long-wave-sensitive (L-) pigment gene followed by one or more middle-wave-sensitive (M-) pigment genes. The expression of these genes to form L- or M-cones is controlled by the proximal promoter and by the locus control region. The high degree of homology between the L- and M-pigment genes predisposed them to unequal recombination, leading to gene deletion or the formation of L/M hybrid genes that explain the majority of the common red–green color-vision deficiencies. Hybrid genes encode a variety of L-like or M-like pigments. Analysis of the gene order in arrays of normal and deutan subjects indicates that only the two most proximal genes of the array contribute to the color-vision phenotype. This is supported by the observation that only the first two genes of the array are expressed in the human retina. The severity of the color-vision defect is roughly related to the difference in absorption maxima (λmax) between the photopigments encoded by the first two genes of the array. A single amino acid polymorphism (Ser180Ala) in the L pigment accounts for the subtle difference in normal color vision and influences the severity of red–green color-vision deficiency.Blue-cone monochromacy is a rare disorder that involves absence of L- and M-cone function. It is caused either by deletion of a critical region that regulates expression of the L/M gene array, or by mutations that inactivate the L- and M-pigment genes. Total color blindness is another rare disease that involves complete absence of all cone function. A number of mutants in the genes encoding the cone-specific α- and β-subunits of the cGMP-gated cation channel as well as in the α-subunit of transducin have been implicated in this disorder.