PITs and FOXes in ocular genetics: the Cogan lecture.

The overall goal of the research in my laboratory is to gain better understanding of the molecular biology of the anterior segment and, in particular, to identify genes that regulate the development and function of this tissue. We have concentrated on discovering and characterizing the genes that, when mutated, cause anterior segment dysgenesis (ASD). ASD encompasses a spectrum of inherited autosomal-dominant diseases that result from maldevelopment of the anterior segment of the eye, with the most serious clinical consequence being that patients have an elevated risk of development of secondary glaucoma. Within the ASD disease spectrum, iris hypoplasia (IH) falls at the mild end, iridogoniodysgenesis (IGD; iris hypoplasia plus goniodysgenesis) is more severe, and AxenfeldRieger (AR) malformations (iris hypoplasia and goniodysgenesis plus corectopia, a prominent and displaced Schwalbe’s line, and adhesions between the iris and the cornea) falls at the most severe end of the spectrum. All conditions can occur with nonocular findings that may include dental, jaw, and umbilical anomalies. Cardiac and pituitary abnormalities have also been reported in patients with anterior segment findings. Glaucoma, associated with elevated IOP has been reported in approximately 50% of patients with AR malformations, and indications are that patients with IGD have greater than a 75% risk of development of glaucoma. In this article I will concentrate on our efforts to improve our understanding of the role in the anterior segment of two genes, PITX2 and FOXC1 (the PIT and FOX of the article’s title).