• This case-control study confirmed that CYP1B1 mutations are associated with primary open-angle glaucoma (POAG) and primary congenital glaucoma (PCG) in Pakistan and identified novel mutations.

    While CYP1B1 is the most commonly mutated gene in PCG, and CYP1B1 mutations have also been identified in POAG, the authors conducted this study to describe mutations in CYP1B1 in Pakistani patients and families with PCG and POAG. Different CYP1B1 mutations have been identified among diverse ethnic groups, some of which may be population specific.

    This study included 40 families, 190 sporadic POAG cases and 140 controls from Pakistan. The researchers genotyped patients and healthy individuals of one consanguineous Pakistani family. They performed direct sequencing of the CYP1B1 gene in probands of the families, sporadic POAG cases and control individuals.

    Homozygosity mapping in the consanguineous family found one 11-Mb homozygous region encompassing the CYP1B1gene and a homozygous CYP1B1 missense mutation (p.Arg390His). Sequence analysis of CYP1B1 in 39 additional families revealed one known and three novel homozygous mutations in PCG (p.Ala288Pro, p.Asp242Ala, p.Arg355* and p.Arg290Profs*37).

    In POAG, the researchers identified one novel heterozygous missense mutation (p.Asp316Val) in one family and a previously reported mutation (p.Glu229Lys) in three families. Analysis of CYP1B1 in a panel of 190 sporadic POAG patients revealed three novel heterozygous variants (p.Thr234Lys, p.Ala287Pro and p.Gln362*) and three previously reported heterozygous variants (p.Gly61Glu, p.Glu229Lys and p.Arg368His). The p.Glu229Lys variant was significantly associated with POAG (P = 0.03; odds ratio 2.49).