Color-deficient cone mosaics associated with Xq28 opsin mutations: A stop codon versus gene deletions

Our understanding of the etiology of red-green color vision defects is evolving. While missense mutations within the long- (L-) and middle-wavelength sensitive (M-) photopigments and gross rearrangements within the L/M-opsin gene array are commonly associated with red-green defects, recent work using adaptive optics retinal imaging has shown that different genotypes can have distinct consequences for the cone mosaic. Here we examined the cone mosaic in red-green color deficient individuals with multiple X-chromosome opsin genes that encode L opsin, as well as individuals with a single X-chromosome opsin gene that encodes L opsin and a single patient with a novel premature termination codon in his M-opsin gene and a normal L-opsin gene. We observed no difference in cone density between normal trichomats and multiple or single-gene deutans. In addition, we demonstrate different phenotypic effects of a nonsense mutation versus the previously described deleterious polymorphism, (LIAVA), both of which differ from multiple and single-gene deutans. Our results help refine the relationship between opsin genotype and cone photoreceptor mosaic phenotype.

Research highlights► Cone density and mosaic regularity is equivalent among multiple- and single-gene deutans. ► Novel stop codon mutation is reported in the M opsin (W149X). ► Absence of normal opsin affects organization of the retinal cone mosaic.