Inherited retinal diseases (IRDs) comprise a diverse group of disorders that frequently lead to progressive vision impairment and blindness. Despite advances in genetic testing, a significant number of IRD cases remain genetically unsolved, often due to unidentified disease-associated genes or variants. This study aims to report additional cases for the newly discovered IRD genes of the AP5-complex. A comprehensive ophthalmological evaluation was performed for all patients, including retinal imaging (multimodal imaging), visual field testing and electroretinogram (ERG) testing. Whole genome and exome sequencing (WGS & WES) were performed for clinically unsolved IRD patients, and data were analyzed to identify underlying causal variants. The identified variants were subsequently validated using Sanger sequencing. Five unrelated patients from Europe and Iran were identified with a distinctive macular degeneration associated with bi- allelic variants in AP5Z1 (HGNC: 22197) and AP5B1 (HGNC: 25104), subunits of the vesicular fifth adaptor protein (AP-5) complex. AP-5 complex is the part of the intracellular trafficking machinery thought to be involved in cellular homeostasis and lysosomal functioning in the retinal pigment epithelium (RPE). The identification of bi-allelic variants in two proteins of AP-5 complex expand the characterization of AP-5 genes in sustaining and preserving normal macular function.
Hussain et al. (Sun,) studied this question.