NPHP1 FULL DELETION CAUSES NEPHRONOPHTHISIS AND A CONE–ROD DYSTROPHY

Abstract: Purpose: To describe in detail the structural and functional phenotype of a patient with cone-rod dystrophy associated with a full deletion of the NPHP1 gene. Methods: A 30-year-old male with history of end-stage renal disease (ESRD) presented with progressive vision loss in early adulthood prompting evaluation for retinal disease. Ophthalmic evaluation was performed including, kinetic fields, electroretinography (ERG), spectral domain optical coherence tomography (SD-OCT), fundus auto-fluorescence (FAF), wide-angle fluorescein angiography and near infrared imaging (NIR). Results: Visual acuity was 20/60 in each eye. Fundus examination revealed a subtle bull’s-eye maculopathy confirmed with fundus autofluorescence. SD-OCT demonstrated perifoveal loss of the outer retinal layers with structural preservation further peripherally. Testing of retinal function confirmed loss of cone greater than rod sensitivities in a manner that co-localized to structural findings. ERG revealed decreased photopic and scotopic 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 upon the growing literature describing retinal disease associated with systemic ciliopathies.