Molecular genetics of primary congenital glaucoma

Molecular genetic studies conducted during the last several years have thro wn some light on the basic molecular defects in primary congenital glaucoma (PCG) and the rationale behind the clinical and genetic presentation of th is paediatric eye condition. The existence of a hereditary form of PCG segr egating as an autosomal recessive trait,vith high penetrance is now confirm ed, The primary molecular defect underlying the majority of PCG cases has b een identified as mutations in the cytochrome P4501B1 (CYP1B1) gene. This g ene is expressed in tissues of the anterior chamber angle of the eye. Molec ular modelling experiments suggest that mutations observed in PCG patients interfere with the integrity of the CYP1B1 molecule as well as its ability to adopt a normal conformation and bind haem. On the basis of these observa tions, we hypothesised that CYP1B1 participates in the normal development a nd function of the eye by metabolising essential molecules that are perhaps used in a signalling pathway. Revealing the identity of this molecule is o ur major objective since it can lead to as yet unknown biochemical cascades controlling the terminal stages of anterior chamber angle development.