Screening for Gene Mutations Associated with Primary Congenital Glaucoma in a Cohort of Palestinian Patients رسالة ماجستير

Abstract

Background: Primary congenital glaucoma (PCG) is a severe childhood ocular disease that can lead to irreversible blindness if not detected and treated early. In Palestine, PCG is more prevalent than global averages, likely due to high consanguinity rates. Currently, diagnosis is only possible after birth, and many affected Palestinian children are diagnosed too late for optimal intervention. The only available treatment in Palestine is surgical. Understanding the genetic basis of PCG in this population is critical for improving early diagnosis and clinical management. Objective: This study aims to investigate the molecular genetic basis of PCG in a Palestinian cohort by screening the CYP1B1 and MYOC genes associated with PCG. Methods: A total of 46 Palestinian PCG patients were recruited from the West Bank between November 1, 2023, and November 1, 2024, with the assistance of ophthalmologists from the German Eye Center and St. John of Jerusalem Eye Hospital and local specialists. Sanger Sequencing was performed to identify CYP1B1 and MYOC variants. Results: Genetic analysis revealed that 22 patients harbored homozygous pathogenic CYP1B1 variants in exons 2 and 3. Nine patients carried heterozygous pathogenic CYP1B1 variants, including one in compound heterozygous form, while 15 were CYP1B1-negative. In total, seven pathogenic variants were identified, one novel and six previously reported. The identified genetic profile closely resembles that of other Arab populations. Conclusion: This study provides the first comprehensive molecular analysis of PCG in the Palestinian population, identifying both novel and previously reported CYP1B1 variants. These findings contribute to a better understanding of PCG genetics and emphasize the need for genetic screening programs to facilitate early diagnosis, targeted interventions, and potential future therapeutic developments.