Genetics and biochemistry of primary congenital glaucoma

Several observations noted by early investigators supported the supposition that in most cases, congenital glaucoma is determined by genetic factors. The genetic heterogeneity of PCG was confirmed by genetic linkage studies conducted in the 1990s when the authors determined that CYP1B1 is the congenital glaucoma gene at the GLC3A locus. The coding sequence of CYP1B1 has been subjected to extensive screening in familial and sporadic cases of glaucoma from numerous countries and from a large number of ethnic groups. These studies have provided evidence for extensive allelic heterogeneity at the GLC3A locus. This article also discusses the molecular evidence for reduced penetrance in congenital glaucoma and the phenotypic heterogeneity of CYP1B1 mutations, mouse models of CYP1B1, and the biochemistry of CYP1B1.