Abstract
Heterozygous mutation of PAX6 in humans leads to congenital aniridia (OMIM 106210) which is typified by congenital iris and foveal defects, and later onset glaucoma, aniridic keratopathy, and cataract. Mice heterozygous for Pax6 mutations phenocopy many aspects of aniridia including the iris defects, keratopathy and cataract, although Pax6 mutant mice have small lenses, a phenotype which is not typically reported in human aniridia, perhaps due to difficulties in measuring lens diameter during typical ophthalmic examinations as the lens periphery is shielded by the iris. In order to overcome this, records of patients diagnosed with congenital aniridia between April 2015 and May 2021 at the Necker-Enfants Malades Hospital, and genetically confirmed with a disease-causing PAX6 variant, were retrospectively reviewed for those with normal axial length whose iris defects allowed visualization of the lens margins and corneal diameter to allow calculation of a lens/corneal diameter ratio. This value was compared with values obtained from a cohort of patients with Sjödell grade IV oculocutaneous albinism type 1 (OCA1; OMIM 203100) which allowed visualization of the lens periphery via iris transillumination. This analysis revealed that patients with congenital aniridia had a significantly lower lens/corneal ratio when compared to those with albinism, suggesting that humans haploinsufficient for PAX6, like mice, rats, frogs, and zebrafish, exhibit reductions in lens size.