Review and Meta-Analysis of BEST1 Retinopathy: Global Prevalence and Mutational Landscape

PURPOSEBEST1-associated inherited retinal disease constitutes one of the largest inherited retinal disease patient populations across the world. Innovative therapies are currently in development to address this significant unmet need. To better understand the scale of unmet need, and the distribution of phenotypes and genotypes, we conducted a meta-analysis of BEST1 patients reported in the literature to provide up-to-date patient number estimates. METHODSWe utilized the GeneScape(R) IRD Patient Atlas, an expertly curated database of [~]73K retinal disease patients undergoing extensive genetic testing, in combination with a dedicated literature search to estimate the proportion of IRD patients attributed to BEST1 using fixed effects weighting. This was also translated to patient number estimates for each country. Further extrapolation of patient subtypes was estimated based on cohorts of BEST1 patients reporting phenotypes and genotypes. In addition, a summary of contributing variants is reported by region. RESULTSAcross regions BEST1 retinopathy patients are estimated to occur from 1 in 38K (in Germany) to 1 in 363K in Japan. In the western countries, bi-allelic patients are expected to contribute nearly 20% of the total BEST1 population, whereas one third of patients in East Asia are anticipated to be bi-allelic. CONCLUSIONSWhile patients are reported across the world, their prevalence and composition vary across geographies. In the literature bi-allelic patients are less often reported explicitly as ARB patients in the United States as compared to Europe. Variant diversity is reflected in regional reports and drives phenotypic distribution.