الملخص الإنجليزي
Glaucoma is an optic neuropathy causing irreversible blindness. The incidence is expected to increase to 79.6 million cases worldwide in the coming years, with Middle Eastern countries having elevated rate as a potential effect of higher consanguineous unions. It is clinically and genetically heterogeneous, thus a genetic profile of this disorder needs to be characterized on a population specific manner. Nine families from the Sultanate of Oman were clinically characterized and recruited into the study. These consisted of four primary congenital glaucoma (PCG) families, three juvenile open angle glaucoma (JOAG) families, a combined phenotypic family with JOAG including PCG (JOAG-PCG), and an adult-onset primary open angle glaucoma (AO-POAG) family. DNA was extracted for the identification of potential causative genetic factors driving the disease. SNP array data was initially produced for a PCG family. Of the homozygous locations identified, regions on chromosome 2 were consequently prioritized due to an influential PCG gene, cytochrome P450 subfamily I polypeptide 1 (CYPIBI). However, sequencing of this gene did not reveal any mutations. Whole exome capture sequencing data was then generated for the remaining eight families. Validation processes of 146 selected variants identified six co-segregating variants, in four genes. CYPIB/ variants (p.G61E and p:D374N) were found in all three PCG families and the p.E229K variant was identified in a JOAG family. Additionally, novel variants in nitric oxide synthase 3 (NOS3), p.G643S, and class II major histocompatibility complex transactivator (CIITA), p.L4771, were found co-segregating separately in two PCG families with CYPIB/variants. In the JOAG-PCG family, a new chemotactic cytokines receptor 5 (CCR5) alteration, p.N48S, was solely indentified. Two variants (CYPIBI: p.E229K and CCR5: p.N48S), in two individuals, asymptomatic at time of enrollment, predicted the presence of the disease in the JOAG and JOAG-PCG families. This highlights the importance of such studies in prospective clinical ramification. CYP1B1 mutations are likely the primary cause of glaucoma in most families. The segregation of the additional variants in NOS3, CIITA and CCR5 genes, and their correlation to previously suggested glaucomatous mechanism possibly implicates them in the disorder. However, these findings warrant further investigations to substantiate their roles in the glaucoma process, Additionally, the remaining four families need to be studied in order to identify potentially novel genes and variants
