PAX6 mutations may be associated with high myopia

PAX6 is a key regulator of eye development and there are many well recognized ophthalmic sequelae of mutations at this locus. The 14 exon <i>PAX6</i> gene is well conserved across species and phyla. Coding region mutations manifest in a variety of phenotypes. Predicted premature protein truncations are generally associated with classical aniridia. Missense mutations are often found in cases with variant phenotypes such as ectopia pupillae; isolated foveal hypoplasia; nystagmus and hyaloid vessel proliferation. The locus has also been implicated, through a genome-wide sib-pair scan, to be important in the normal variation of myopia. We investigated the association between identified <i>PAX6</i> mutations and refractive error in Australian patients from four pedigrees. Two of eight subjects with a 1410delC <i>PAX6</i> mutation had a mean spherical equivalence < -9D, whilst a mean spherical equivalence ≤ -5D was recorded in two from four subjects with an Arg240Stop <i>PAX6</i> mutation and one of two subjects with a Glu93Stop mutation. One individual identified with a Pro346Ala PAX6 mutation had a mean spherical equivalence of +2.8 D. Thus, our observations generally support other incidental findings, that <i>PAX6</i> mutation, particularly predicted haploinsufficiency, may be associated with extreme refractive error, although the mechanism by which this occurs is not clear.