Characterization of the genetic landscape of hereditary retinopathies in Pakistan

Hereditary retinopathies (HRPs) are a group of rare Mendelian disorders often leading to progressive vision loss and potential blindness. Despite their monogenic nature, HRPs exhibit extensive genetic heterogeneity, with pathogenic variants identified in nearly 300 genes. In this study, we investigated the genetic landscape of HRPs in Pakistan, a population with high consanguinity and unique demographic features. A cohort of 213 families (722 affected individuals) underwent genetic analysis, primarily through whole-exome sequencing, achieving a molecular diagnosis in 80.3% of cases. Pathogenic or likely pathogenic variants were identified in 60 HRP-associated genes, with ABCA4, CRB1, MYO7A, PDE6B, and RP1 being the most prevalent. The findings underscore a distinct mutational spectrum, shaped by endogamy and recurrent founder mutations, differing from other populations.