In order to study the DNA methylation status of the putative promoter of the Pax6 gene in embryos with ocular malformations, an exploratory study was carried out in which DNA was isolated from embryos with anophthalmia, microphthalmia, and cyclopia, as well as from their normal counterparts.
The wide variability of ocular phenotype regardless of the presence or absence of PAX6 mutations calls for a further appreciation of the complexity in the molecular diagnosis of aniridia and suggests that this ocular malformation may be better regarded as a group of heterogeneous disorders, rather than a single disease entity, associated with mutations in PAX6 and/or other genes located elsewhere in the human genome.
In humans, PAX6 is located in chromosome 11p13, and its mutations lead to a variety of hereditary ocular malformations of the anterior and posterior segment, among which aniridia and most probably foveal hypoplasia are the major signs.
This finding demonstrated that the frequency of PAX6 mutations associated with optic nerve malformation is low, requiring the elucidation of other candidate genes in other patients.
A variety of PAX6 gene mutations were identified in patients with aniridia and/or allied ocular dysgenesis such as keratopathy, Peters' anomaly, foveal hypoplasia, and nystagmus.
Some mutations that interrupt pathways early in development will cause malformations that are static or nonprogressive, as seen in PAX6 and Shh mutations.
The finding that mutations in PAX6 underlie ADK, along with a recent report that mutations in PAX6 also underlie Peters anomaly, implicates PAX6 broadly in human anterior segment malformations.
The pattern of malformations is similar to that in homozygous Sey mice and suggests a critical role for PAX6 in controlling the migration and differentiation of specific neuronal progenitor cells in the brain.