Abstract
Purpose: :
To study cone photoreceptor structure and function in patients with enhanced S-cone syndrome caused by compound heterozygous mutations in the NR2E3 gene.
Methods: :
The coding sequences of the NR2E3 gene were bidirectionally sequenced in 2 patients from a family with the clinical diagnosis of enhanced S-cone syndrome. Adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography (SDOCT) images were obtained and compared with normals. Visual acuity (VA), color vision, and full-field (ffERG) and multifocal electroretinography (mfERG) were also measured.
Results: :
Molecular analysis revealed compound heterozygous mutations in NR2E3 in a 59 year-old woman (Arg125Stop and Tyr209Stop) and her 35 year-old nephew (Arg125Stop and Arg77Trp). Retinal pigment epithelial atrophy was present in the macula of the aunt and along the arcades in both patients. VA was 20/32 in the nephew and 20/200 in the aunt. Color vision was normal in the nephew but abnormal in the aunt. ffERG in both patients showed unmeasurable responses to rod-mediated stimuli, with large, negative waveforms to bright stimuli presented under both scotopic and photopic conditions. mfERG amplitudes were reduced with delayed timing in the nephew and unmeasurable in the aunt. SDOCT of the nephew showed a thickened outer nuclear layer outside the fovea and abnormal inner and outer segments beyond 20. The aunt had outer segment layer loss with foveal sparing, loss of lamination of the outer nuclear and outer plexiform layer, and inner retinal thinning. In the nephew, AOSLO showed contiguous patches of cones interspersed with less resolved structure. Cones were less dense than normal at the foveola, but by 2 deg the density was greater than normal and were relatively constant with eccentricity. By 10 deg, the cone density was about 4X greater than normal. However, the cone density remained about 4X lower than the highest density of combined photoreceptors (rods and cones) in a normal eye. The aunt had more extensive cone loss but patches of greater than normal cone density were present.
Conclusions: :
AOSLO revealed cones with supernormal density in patients with enhanced S-cone syndrome caused by mutations in NR2E3, consistent with an excess of S-cones in the absence of intervening rod photoreceptors.
Keywords: retinal degenerations: hereditary • imaging/image analysis: clinical • photoreceptors