CYP1B1 Mutations in South Korean Patients With Primary Congenital Glaucoma : Genotype - Phenotype Correlations

Abstract

Purpose: : To investigate the incidence of CYP1B1 (cytochrome P4501B1) mutations in South Korean patients with primary congenital glaucoma (PCG) and establish the genotype-phenotype correlations.

Methods: : Total 96 patients with PCG and 100 normal subjects were analyzed for mutations by direct sequencing of polymerase chain reaction fragments. Patients were classified into Group 1 (no mutation) or Group 2 (mutations). We compared the phenotypes based on the severity index (SI: normal to severe/very severe) and the responses to treatment of the two groups.

Results: : 9 mutations were identified in 22 patients (22.9%) : 7 patients had 2 mutations (3 homozygote, 4 compound heterozygote) and 15 patients had 1 mutation. 5 mutations were novel mutations. The proportions of bilateral involvement (85.7%) and early-onset PCG (95%) in group 2 (n=21) were higher than those (63.3%, 63.3%) in group 1 (n=60)(p>0.05). In the baseline and final SI, the proportions of severe/very severe cases in group 2 (71.4%, 42.1%) was higher than those in group 1 (42.1%, 30.4%)(p>0.05). Further, the incidence of severe complications and the number of surgical interventions in group 2 were higher than the corresponding values in group 1(p<0.05).

Conclusions: : Less than a quarter of South Korean PCG patients possess CYP1B1 mutations. The finding that 15.6% patient had 1 mutation implies the existence of unknown mutations that cannot be detected by standard methods or are located in promoter or intron regions. In patients with mutations, the symptoms or signs tended to occur earlier on both eyes than in the patients without mutations; moreover, patients with mutations showed poor response to treatment.

Keywords: gene screening • clinical (human) or epidemiologic studies: prevalence/incidence • clinical (human) or epidemiologic studies: natural history