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Purpose: To describe in detail the structural and functional phenotypes of a patient with cone-rod dystrophy associated with a full deletion of the NPHP1 gene., Methods: A 30-year-old man with a history of end-stage renal disease presented with progressive vision loss in early adulthood prompting evaluation for retinal disease. Ophthalmic evaluation was performed including visual fields, electroretinography, spectral domain optical coherence tomography and short-wavelength and near-infrared fundus autofluorescence imaging., Results: The visual acuity was 20/60 in each eye. Fundus examination revealed a subtle bull's-eye maculopathy confirmed with fundus autofluorescence. Spectral domain optical coherence tomography demonstrated perifoveal loss of the outer retinal layers with structural preservation further peripherally. Static perimetry confirmed the loss of cone greater than rod sensitivities in a manner that colocalized to structural findings. Electroretinography revealed decreased cone- and rod-mediated responses. Genetic testing confirmed a homozygous whole-gene deletion of the NPHP1 gene., Conclusion: NPHP1 -associated retinal degeneration may present as a cone-rod dystrophy in addition to the previously reported rod-predominant phenotypes and can notably be associated with systemic abnormalities, including renal disease. Our work further expands on the growing literature describing the retinal disease associated with systemic ciliopathies.

Purpose : To provide a detailed ophthalmic phenotype of two male patients with Bardet-Biedl Syndrome (BBS) due to mutations in the BBS7 gene Methods : Two brothers ages 26 (Patient 1, P1) and 23 (P2) underwent comprehensive ophthalmic evaluations over three years. Visual function was assessed with full-field electroretinograms (ffERGs), kinetic and chromatic perimetry, multimodal imaging with spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF) with short- (SW) and near-infrared (NIR) excitation lights and adaptive optics scanning light ophthalmoscopy (AOSLO). Results : Both siblings had a history of obesity and postaxial polydactyly; P2 had diagnoses of type 1 Diabetes Mellitus, Addison's disease, high-functioning autism-spectrum disorder and -12D myopia. Visual acuities were better than 20/30. Kinetic fields were moderately constricted. Cone-mediated ffERGs were undetectable, rod ERGs were ~80% of normal mean. Static perimetry showed severe central cone and rod dysfunction. Foveal to parafoveal hypoautofluorescence, most obvious on NIR-FAF, co-localized with outer segment shortening/loss and outer nuclear layer thinning by SD-OCT, and with reduced photoreceptors densities by AOSLO. A structural-functional dissociation was confirmed for cone- and rod-mediated parameters. Worsening of the above abnormalities was documented by SD-OCT and FAF in P2 at 3 years. Gene screening identified compound heterozygous mutations in BBS7 (p.Val266Glu: c.797 T > A of maternal origin; c.1781_1783delCAT, paternal) in both patients. Conclusions : BBS7 -associated retinal degeneration may present as a progressive cone-rod dystrophy pattern, reminiscent of both the murine and non-human primate models of the disease. Predominantly central retinal abnormalities in both cone and rod photoreceptors showed a structural-functional dissociation, an ideal scenario for gene augmentation treatments.