Genotype/Phenotype Correlation in Primary Congenital Glaucoma Patients in the Lebanese Population: A Pilot Study

Background: The incidence of primary congenital glaucoma (PCG) varies among geographic regions and ethnic groups. The frequency of PCG in Lebanon and identification of disease-causing mutations have not been studied previously.

Purpose: To investigate the role of Cytochrome P1B1 (CYP1B1) gene and Myocillin (MYOC) gene mutations in PCG in the Lebanese population and study possible genotype/phenotype correlations.

Methods: Patients with unilateral or bilateral PCG diagnosed at the American University of Beirut Medical Center and their first-degree relatives (parents and siblings) were screened for CYP1B1 and MYOC mutations. Demographic and phenotypic characteristics were recorded. Phenotypic characteristics pertaining to disease severity and outcomes were compared.

Results: Eighteen Lebanese families (66 subjects) with at least one member affected with PCG were included in this study. Mutations in the CYP1B1 gene were detected in 6 families (33%). Five previously described mutations (p.R444Q; p.E229K; p.R469W; p.G61E; p.M1T) and one new single nucleotide deletion were identified (1793delC). Patients in whom CYP1B1 mutations were detected tended to have a more severe phenotype as evidenced by earlier age at diagnosis, higher rate of bilateral disease, and higher number of glaucoma surgeries than those in whom no CYP1B1 mutations were present. MYOC gene mutations were not detected in any patients.

Conclusion: The rate of CYP1B1 mutations in Lebanese patients with PCG is lower than that reported in other Arab and Middle Eastern populations and suggests other genes are responsible for PCG in the remainder.