Variant-specific disruption to Notch signaling in PAX6 microphthalmia and aniridia patient-derived hiPSC optic vesicles [ATAC-Seq]

The homeobox-containing transcription factor PAX6 is a key regulator of eye development. Pathogenic heterozygous PAX6 variants lead to variable ocular phenotypes. Missense variants are often associated with milder ocular conditions, although variants in the DNA-binding paired domain which alter target binding lead to severe ocular phenotypes including bilateral microphthalmia, similar to SOX2 anophthalmia syndrome. However, the variant-specific pathway disruption resulting in phenotypic heterogeneity is not well understood. Chromatin accessibility using ATAC-seq was carried out on Aniridia (PX and AN) and wildtype control iPSC derived 3D retinal organoids at timepoints day 35, two clonal lines per condition, two replicates per clone.