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Background: CYP1B1 is the most commonly mutated gene in primary congenital glaucoma (PCG), and mutations have also been identified in primary open-angle glaucoma (POAG). This study was undertaken to describe mutations in CYP1B1 in patients and families with PCG and POAG from Pakistan.

Design: Case-control series.

Participants: Forty families, 190 sporadic POAG cases and 140 controls from Pakistan.

Methods: Patients and healthy individuals of one consanguineous Pakistani family were genotyped with high-resolution single nucleotide polymorphism microarrays. Homozygosity mapping was performed using Homozygosity Mapper. Direct sequencing of CYP1B1 gene was performed in probands of the families, sporadic POAG cases and control individuals.

Main Outcome Measures: Mutations in the CYP1B1 gene in PCG and POAG patients.

Results: Homozygosity mapping in a consanguineous Pakistani family revealed one 11-Mb homozygous region encompassing the CYP1B1 gene. A homozygous CYP1B1 missense mutation (p. Arg390His) was identified in this family. 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, one novel heterozygous missense mutation (p. Asp316Val) was identified in one family and a previously reported mutation (p. Glu229Lys) was identified 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 …