Glaucoma is the most common cause of irreversible blindness worldwide. Primary congenital glaucoma (PCG) is a subgroup with severe manifestations and childhood onset. Earlier studies had shown that CYP1B1 mutations are cause of disease in approximately 70% of Iranian patients, that most of the patients originate from the west or north-west regions of Iran, and that four CYP1B1 mutations (p.Arg368His, p.Arg469Trp, p.Arg390His, and p.Gly 61Glu) constitute most of the mutated alleles of Iranian patients. We aimed in this study to get a relatively reliable estimate of frequency carriers of the four common mutations in Gilan. Preliminary data had identified Gilan as one of the provinces with a relatively high prevalence of PCG.

700 individualsfrom Gilan, selected with considerations of population based epidemiologic studies, were screened for the four mutations using PCR-RFLP or PCR-ARMs protocols. Mutations observed were validated by Sanger sequencing.

Four carriers of p.Gly61Glu, one person homozygous for p.Gly61Glu, and seven carriers of p.Arg368His were identified. At the 95% confidence level, at least 0.3% and at most 0.9% of the Gilan population carry one of the two mutations. Most of the mutated p.Gly61Glu and p.Arg368His alleles were, respectively, found in Talesh and the eastern regions of Gilan. Appropriate calculations suggest that at the 95% confidence level, the frequency of the p.Gly61Glu carriers in the Talesh region is between o.8% and 7.3%. Similarly, the frequency of p.Arg368His carriers in the eastern regions of Gilan is between 0.8% and 4.8%. P.Arg390His and p.Arg469trp were not observed in Gilan.

The findings suggest that p.Gly61Glu and p.Arg368His CYP1B1 alleles are relatively frequent in Gilan and that they are not randomly distributed in Gilan; they seem to be concentrated in Talesh and the eastern regions of Gilan.In order to validate these findings, larger cohorts from Talesh and the eastern regions of Gilan need to be screened. As national frequencies of mutations may not correspond to frequencies at province levels, and that frequencies may vary in different regions within a province, CYP1B1 mutation screening need to done in the seven provinces earlier identified as having high incidence of PCG.