Screening of Inherited Retinal Disease Patients in a Low‐Resource Setting Using an Augmented Next‐Generation Sequencing Panel

Abstract

ABSTRACT Background Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of disorders affecting millions worldwide. Despite the widespread adoption of next‐generation sequencing (NGS) panels, there remains a critical gap in the genetically diverse and understudied African populations. Methods One hundred and thirty‐five South African patients affected by various IRDs underwent NGS using a custom‐targeted panel sequencing over 100 known genes. The panel was supplemented by in silico screening for a MAK‐Alu insertion and screening of seven functionally established deep intronic variants. Results Through our combined screening strategy, we obtained a probable genetic diagnosis for 56% of the cohort. We identified 83 unique variants in 29 IRD genes underlying the disease, including 16 putative novel variants. Molecular findings prompted recommendations for clinical re‐examination in ten patients. Resolution rates varied across clinical classifications and population groups. Conclusions This study reports the first use of a targeted NGS panel for IRDs in southern Africa, demonstrating a cost‐effective, customisable approach that optimises both diagnostic yield and resource efficiency, making it a valuable tool for IRD molecular characterisation in resource‐limited settings. Augmenting the panel by screening for variants relevant to South African patients allowed us to achieve a resolution rate in line with international studies. Our study underscores the importance of investigating diverse populations to bridge disparities in genomic research and improve diagnostic outcomes for underrepresented population groups.

Keywords

• deep intronic variants
• inherited retinal disease
• targeted next‐generation sequencing