Studies On The Molecular-Genetics Of Tritanopia

Tritanopia differs fundamentally from other inherited anomalies of color vision. Its autosomal dominant tranmission1 implies a mechanism unlike that of protanopia or deuteranopia. Because people with tritanopis lack a measurable blue-cone electroretinographic response,2 the defect is likely localized within blue-cone photoreceptors. These findings suggest that a mutant gene product actively interferes with blue-cone function or viability. Could a mutation in the gene encoding the blue-sensitive visual pigment3 be responsible for tritanopia? To test this hypothesis we have used the polymerase chain reaction and denaturing gradient gel electrophoresis to screen for sequence variation in this gene in members of five families in which tritanopia appears in more than one generation. We have found three different single-nucleotide changes in affected members of four families that were not detected in control subjects of appropriate ancestry (p = 0.001, p = 0.003, and p = 0.003, respectively). Two of the changes encode different singleamino-acid substitutions and the third, a single-nucleotide deletion, disrupts a sequence likely to be important for proper splicing of messenger RNA. Expression studies of visual-pigment DNA constructs bearing these sequence alterations are in progress.