PAX6

Investigation of the molecular pathology of oculogenesis regulator, PAX6, through patient-derived hiPSC optic vesicles with (i) haploinsufficiency-related aniridia and (ii) missense-associated microphthalmia. Transcriptomic analysis reveals variant-specific disruption to SOX2-mediated Notch-signalling perturbing proliferation and differentiation, uncovering a mechanism for PAX6-associated microphthalmia.

PAX6 is considered the master regulator of eye development, the majority of variants affecting this gene cause the pan-ocular developmental eye disorder aniridia. Although no genotype-phenotype correlations are clearly established, missense variants affecting the DNA-binding paired domain of PAX6 are usually associated with non-aniridia phenotypes like microphthalmia, coloboma or isolated foveal hypoplasia. In this study, we report …