This natural history study of patients with PCDH15 disease-causing variants will accelerate the development of outcome measures for clinical trials. Sensitive, reliable outcome measures of retinal degeneration will greatly facilitate development of treatments for retinitis pigmentosa due to PCDH15 disease-causing variants. Together these approaches are expected to have an impact on understanding PCDH15 related retinal degeneration, developing experimental treatment protocols, and assessing their effectiveness.~The goals and expected impact of this natural history study are to:~Describe the natural history of retinal degeneration in patients with biallelic disease-causing variants in the PCDH15 gene~Contribute to the identification of sensitive structural and functional outcome measures to use for future multicenter clinical trials in PCDH15 related retinal degeneration~Contribute to the identification of populations for future clinical trials of investigative treatments for PCDH15 related retinal degeneration~Study Objectives~The primary objectives of the natural history study are to:~Characterize the natural history of retinal degeneration associated with biallelic pathogenic mutations in the PCDH15gene over 4 years, as measured using functional, structural, and patient-reported outcome measures~Explore whether structural outcome measures can be validated as surrogates for functional outcomes in individuals with biallelic pathogenic mutations in the PCDH15 gene~Explore possible risk factors (genotype, phenotype, environmental, and comorbidities) for progression of the outcome measures at 4 years in individuals with biallelic pathogenic mutations in the PCDH15 gene~Explore variability and symmetry of left and right eye outcomes over 4 years in individuals with biallelic pathogenic mutations in the PCDH15 gene
The overall goal of this project, co-funded by the Foundation Fighting Blindness and the USHER 1F Collaborative is to characterize the natural history of disease progression in patients with PCDH15 mutations in order to accelerate the development of outcome measures for clinical trials.