Inherited Retinal Dystrophies in Spain: three decades of epidemiological, clinical, and genetic study

Inherited Retinal Dystrophies (IRDs) are a group of rare diseases with prevalence 1:3000-4000 people. They genetic, primarily affecting retinal photoreceptors and epithelial pigmentary cells, lead to neurodegeneration finally apoptosis. In 2021, we published our global results obtained in registry at the Fundación Jiménez Díaz University Hospital (Madrid, Spain) from 1991 August 2019. Now, aimed update these until 2022. Thus, conducted retrospective hospital-based cross-sectional study on 4.794 IRD-affected unrelated families all Spanish autonomous communities. Families were classified into three phenotypic categories: a) “NON-RP” for cone-dominated phenotypes, b) “RP” (retinitis pigmentosa) primary rod involvement, c) “syndromic IRD” when visual plus extra-ocular symptoms present. Molecular studies included: single-gene studies, clinical exome, whole exome or genome sequencing. Overall, 62% (2962/4794) genetically characterized, which 1.997 different likely causative variants (5.064 alleles) identified 188 genes. The most common phenotype encountered was RP (59% families, 2465/4794). Regarding types alleles, missenses frequent (51%), followed by truncating (nonsense, frameshift, indels splicing; 44%), while copy number variations only 2%. recurrently mutated genes PRPH2, ABCA4 RS1 autosomal dominant (AD), recessive (AR) X-linked (XL) NON-RP respectively; RHO, USH2A RPGR AD, AR XL non-syndromic RP; MYO7A, BBS1 syndromic IRD. Pathogenic ABCA4:p.Arg1129Leu USH2A:p.Cys759Phe frequent. Our provides overall genetic landscape IRD Spain, reporting largest cohort ever presented high causal involved diseases. Furthermore, findings have important implications diagnosis counseling, but also possible therapeutic management