Mutation spectrum of CYP1B1 and MYOC genes in Korean patients with primary congenital glaucoma

PURPOSE To elucidate the incidence of cytochrome P450 1B1 (CYP1B1) and myocillin (MYOC) mutations in Korean patients with primary congenital glaucoma (PCG). METHODS Genomic DNA was collected from peripheral blood of 85 unrelated Korean patients who were diagnosed as having PCG by standard ophthalmological examinations and screened for mutations in the CYP1B1 and MYOC genes by using bi-directional sequencing. RESULTS Among 85 patients with PCG, 22 patients (22/85; 25.9%) had either one (n=11) or two (n=11) mutant alleles of the CYP1B1 gene. Among 11 different CYP1B1 mutations identified, a frameshift mutation (c.970_971dupAT; p.T325SfsX104) was the most frequent mutant allele (6/33; 18.2%) while p.G329S and p.V419Gfs11X were novel. In the MYOC gene, two variants of unknown significance (p.L228S and p.E240G) were identified in two PCG patients (2/85; 2.4%), respectively. No patient had mutations in both genes. CONCLUSIONS Although CYP1B1 mutations are major causes of PCG in Korea, ~70% of PCG patients have neither CYP1B1 nor MYOC mutations suggesting a high degree of genetic heterogeneity. Furthermore, the fact that 11 out of 22 patients had only one mutant allele in the CYP1B1 gene necessitates further investigation for other genetic backgrounds underlying PCG.