Aniridia

Developmental defects in the embryonic eye are a significant cause of blindness in Canada. These defects, which include Aniridia, often have a very strong genetic link.

Aniridia, a Latin word meaning "without iris", is a rare condition that results in the underdevelopment of the iris and poor development of the retina at the back of the eye, causing partial or complete blindness. Several years ago, researchers have discovered that a large proportion of Aniridia is caused by a single malfunctioning gene called PAX6. Disruption of a single copy of the PAX6 gene can block the migration of cells that form the iris, resulting in the disease.

Our Research

We are working to characterize gene regulatory networks in the developing eye and the consequences of their perturbations, while focusing our efforts to study two key genes—PAX6 and NR2E1—that play a crucial role in eye development and the formation of disease.

While the PAX6 gene has been known to explain about 80% of all cases of Aniridia, the cause of the remaining 20% has remained a mystery. We hypothesize that the NR2E1 gene is a master regulator of eye development and that the malfunctioning of this gene can result in Aniridia.

With the help of cutting-edge genotyping technology, we are currently performing a deep sequencing project on over 50 human patient DNA samples of patients with Aniridia who possess no identified PAX6 mutations. Through this process, we aim to elucidate NR2E1's potential involvement in the development of Aniridia. Based on the results of this study, we hope to design an additional marker for screening of Aniridia in patients who do not carry the crucial PAX6 mutations.

For further information about Aniridia you can visit the Aniridia website on PFOND, an online portal that promotes the sharing of information regarding research, treatment and resources for rare genetic disorders.

Publications

Kumar RA, Leach S, Bonaguro R, Chen J, Yokom DW, Abrahams BS, Seaver L, Schwartz CE, Dobyns W, Brooks-Wilson A, Simpson EM. Mutation and evolutionary analyses identify NR2E1-candidate-regulatory mutations in humans with severe cortical malformations. Genes Brain Behav. 6(6):503-16. (2007) PMID 17054721