Language

English

Publication Date

4-9-2026

Journal

Human Genetics and Genomics Advances

DOI

10.1016/j.xhgg.2026.100584

PMID

41830174

PMCID

PMC13050037

PubMedCentral® Posted Date

3-12-2026

PubMedCentral® Full Text Version

Post-print

Abstract

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 reports additional cases for the newly discovered IRD genes of the AP-5 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 and 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. The 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 the AP-5 complex expand the characterization of AP-5 genes in sustaining and preserving normal macular function.

Keywords

Humans, Retinal Degeneration, Alleles, Female, Male, Genetic Predisposition to Disease, Exome Sequencing, Pedigree, Mutation, Genetic Variation, inherited retinal diseases, unresolved, whole-genome sequencing, AP-5 complex, AP5Z1, AP5B1

Published Open-Access

yes

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