Deletion of the X-linked opsin gene array locus control region (LCR) results in disruption of the cone mosaic

Abstract

Blue-cone monochromacy (BCM) is an X-linked condition in which long- (L−) and middle- (M−) wavelength-sensitive cone function is absent. Due to the X-linked nature of the condition, female carriers are spared from a full manifestation of the associated defects but can show visual symptoms, including abnormal cone electroretinograms. Here we imaged the cone mosaic in four females carrying an L/M array with deletion of the locus control region, resulting in an absence of L/M opsin gene expression (effectively acting as a cone opsin knockout). On average, they had cone mosaics with reduced density and disrupted organization compared to normal trichromats. This suggests that the absence of opsin in a subset of cones results in their early degeneration, with X-inactivation the likely mechanism underlying phenotypic variability in BCM carriers.

Imaging retinal mosaics in the living eye

“…7,6 Adaptive optics imaging of persons with mutations in the genes that encode the cone opsins have provided new insights about the cone mosaic. [8][9][10] Genetic techniques can determine specific mutations in the cone opsin, revealing the genotype of the affected individual. Adaptive optics imaging can then evaluate the retinal phenotype and examine variation among individuals with the same genotype.…”

Human Cone Visual Pigment Deletions Spare Sufficient Photoreceptors to Warrant Gene Therapy

“…These mutations would be expected to result in complete absence of L-/M-cone opsin expression (Wang et al, 1992). A clue about possible effects of such mutations came with the finding of abnormal cone mosaics in carrier females (Carroll et al, 2010). We evaluated the retinal structure and function in BCM caused by such large deletion mutations, and weighed the value and goals of gene augmentation as a therapy for such patients.…”

Evolutionary history and adaptive significance of the polymorphic Pan I in migratory and stationary populations of Atlantic cod (Gadus morhua)

“…Here we showed that the cod rho gene contains four NRL motifs in the distal region (see Fig. S1), which is probably involved in opsin gene expression in mammals (Carroll et al, 2010). Alternatively, Pan I is expressed in the eye and might interact with rhodopsin to affect visual perception relevant in differential habitat seeking and utilization.…”