Complex Genetics of Glaucoma: Defects in CYP1B1, And Not MYOC, Cause Pathogenesis in an Early-onset POAG Patient with Double variants at both loci

Glaucoma is the second largest cause of blindness worldwide, affecting almost 60 million people (Quigley and Broman 2006). Defects in MYOC and CYP1B1 have been implicated in primary open angle glaucoma (POAG) and primary congenital glaucoma (PCG), respectively. Variants in both the genes have been detected in both the diseases indicating a higher complexity in the pathogenesis of the disease. In this context, we present here the case of a POAG patient who is found to be a compound heterozygote for CYP1B1 mutations and a homozygote for MYOC variant. None of the three nonsynonymous changes were found in 170-unrelated controls with matched age and ethnicity. Analysis of the family members reveal that proband’s younger sister, not affected, was homozygous for the MYOC variant but lacked one variant in CYP1B1. This is in contrast to other reports that showed implication of CYP1B1 in POAG. This case is unique, since both parents of the proband do not show any symptom of POAG, despite of having one defective allele for both MYOC and CYP1B1