Blue Cone Monochromacy Caused by the C203R Missense Mutation or Large Deletion Mutations

To compare the phenotype of blue cone monochromacy (BCM) caused by large deletion mutations with those having the C203R missense mutation.

BCM patients with large deletion mutations (n = 21; age range, 5-60 years), and with the C203R missense mutation (n = 13; age range, 5-70 years), were studied with optical coherence tomography, visual acuity, and perimetric sensitivity in a retrospective observational case series. Perceptual estimates of spatial resolution driven by rods, S-cones, and L/M-cones were obtained by the choice of chromatic gratings presented on varied adapting conditions with a modified microperimeter.

Both genotypes had abnormal foveal photoreceptor structure early in life. Patients with the C203R mutation, however, had decades-longer persistence of foveal photoreceptor outer nuclear layer thickness and a slower rate of development of inner segment/outer segment defects than did patients with large deletion mutations. At late ages, both genotypes had comparably severe losses of central structure. At the rod-rich hot spot, there was no difference in structure between cohorts with age. Grating acuities in all BCM patients were driven by S-cones and rods; the foveal structural differences were not reflected in a difference between cohorts in visual sensitivity and spatial resolution.

A difference in structural phenotype due to the C203R mutation versus large deletion mutations in BCM was detected as a more prolonged persistence of foveal photoreceptor structure in patients with the missense mutation. This should be taken into account in planning natural history studies, selecting outcomes for clinical trials, and defining the time window for possible therapies.