Genetic Study On Primary Open Angle Glaucoma

Primary open-angle glaucoma (POAG) is an important hypotype of glaucoma, a nonreversible blindness and a global public health issue. Epidemiological, medical genetic and molecular genetic investigations indicate that hereditary factors may play an important role in the pathogenesis of POAG. The MYOC, OPTN, CYP1B1 and WDR36 genes are shown to be associated with POAG To define the pathogenesis of POAG, the paper analysed a POAG family pedigree, focusing on genetic mutations in the MYOC, OPTN, CYP1B1 and WDR36 genes. The clinical information of the POAG family members, including their general eye examinations such as visual acuity and refraction, slit lamp examination, direct or indirect ophthalmoscopy, perimetry, intraocular pressure and angle mirror inspection was collected. At the same time, mutations in all exons and partial promoters of the MYOC, OPTN, CYP1B1 and WDR36 genes from the blood genomic DNA of the POAG family members were investigated through PCR amplifying and followed sequencing. Subsequently, influence of mutations of these genes in development of POAG and on physicochemical properties and structural changes of MYOC, OPTN, CYP1B1 and WDR36 were analysed by bioinformatics method.The POAG family investigated is comprised of five generations,46 persons in total,26 male,20 female. And 6 cases including two male and four female patients (one of them died) were diagnosed as POAG in the family. Interestingly, the POAG patients were found in four consecutive generations. The overall incidence of POAG in this family was 13%, of which 4.3% was male and 8.7% was female. Female POAG patients were more than male, existing in three consecutive generations. The results indicate that the POAG is an autosomal genetic disease.The patient â…¢ had a mutation from G to T in the MYOC exon 1, leading to a change from glutamine to histidine at 19 (Q19H). The patient â…¡1, â…¢ 1, â…¢9 and â…£3 were found to have a change from G to C at -927 in the promoter region of MYOC gene. The mutation was not found previously, and detected only in those patients, but not in healthy persons in the family investigated. Patient â…¡1, â…¢1, â…¢9 were found to have a mutation from G to A at the site of 34 in the OPTN exon 4, which does not result in a change in amino acid (T34T). The Q19H and T34T mutations were reported previously in the POAG patient, but not found in healthy control group in the study. Mutation in all exon regions of both CYP1B1 and WDR36 genes was not found. Bioinformatic analysis showed that some slight changes in physicochemical properties of the mutated MYOC protein were found. However, the secondary and spatial structure of the mutated MYOC protein had no change. The C>G mutation at-927 in the promoter region is near to TATA box which was predicted by eukaryotic promoter database (EPD). This mutation may take part in POAG development through affecting MYOC transcription, but mechanism behind is not clear. Bioinformatics analysis showed that the Q19H mutation was in signal peptide of MYOC. The signal peptide could be cut away after going through cell membrane so that the Q19H mutation did not affect the secondary and spatial structures of the MYOC protein. The T34T mutation in the OPTN protein is in agreement with previous reports, and may be involved in POAG development. Not surprisingly, bioinformatics analysis showed that there was no change in physicochemical properties as well as secondary and spatial structures of the mutated OPTN protein. The results mentioned suggest that mutation analysis in those proteins may predict the disease at younger age of the POAG patients.