Identification of novel CYP1B 1 gene mutations in patients with primary congenital and primary open‐angle glaucoma

Background CYP1B 1 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 CYP1B 1 in patients and families with PCG and POAG from P akistan. Design Case‐control series. Participants Forty families, 190 sporadic POAG cases and 140 controls from P akistan. Methods Patients and healthy individuals of one consanguineous P akistani family were genotyped with high‐resolution single nucleotide polymorphism microarrays. Homozygosity mapping was performed using H omozygosity M apper. Direct sequencing of CYP1B 1 gene was performed in probands of the families, sporadic POAG cases and control individuals. Main Outcome Measures Mutations in the CYP1B 1 gene in PCG and POAG patients. Results Homozygosity mapping in a consanguineous P akistani family revealed one 11‐Mb homozygous region encompassing the CYP1B 1 gene. A homozygous CYP1B 1 missense mutation (p. Arg390H is) was identified in this family. Sequence analysis of CYP1B 1 in 39 additional families revealed one known and three novel homozygous mutations in PCG ( p.Ala288P ro, p.Asp242A la, p.A rg355* and p.Arg290P rofs*37). In POAG , one novel heterozygous missense mutation ( p.Asp316V al) was identified in one family and a previously reported mutation ( p.Glu229L ys) was identified in three families. Analysis of CYP1B 1 in a panel of 190 sporadic POAG patients revealed three novel heterozygous variants ( p.Thr234L ys, p.Ala287P ro and p.G ln362*) and three previously reported heterozygous variants ( p.Gly61G lu, p.Glu229L ys and p.Arg368H is). The p.Glu229L ys variant was significantly associated with POAG ( P  = 0.03; odds ratio 2.49). Conclusions This study confirms that CYP1B 1 mutations are associated with POAG and PCG in the P akistani population.