PHENOTYPE/GENOTYPE CORRELATION IN A FAMILY PEDIGREE WITH THE ARG433CYS MUTATION IN THE MYOC GENE

V.P Costa, J. Vasconcellos, M. Melo, R. Schimiti, F. Costa

Department of Ophthalmology, University of Campinas, Brazil

Phenotipe/Genotype Correlation in a Family Pedigree with the Arg433Cys Mutation in the MYOC gene. Vasconcellos JPC, Melo MB, Schimiti RB, Costa F, Costa VP. University of Campinas, Brazil.

Objectives: To evaluate the phenotype/genotype correlation in a family pedigree with primary open angle glaucoma (POAG) carrying the Arg433Cys mutation in the Myocilin (MYOC) gene. Methods: POAG was defined as untreated intraocular pressure (IOP) over 21 mmHg, with characteristic optic nerve and visual field glaucomatous damage. Genomic DNA was collected from peripheral blood. PCR, SSCP and sequencing analysis were performed to identify the presence of Arg433Cys mutation in family members. Results: Forty-four members of this family were evaluated for the presence of the mutation and 15 (34%) were found to harbor it. Among them, 9 (60%) had POAG. None of the 29 individuals without the mutation had glaucoma. The IOP level was significantly higher in individuals harboring the mutation (p<0,0001). Mutation’s penetrance was 0% under 10 years of age (0/2), 40% in individuals from 11-30 years (2/5), 87% above 30 years (7/8), and 100% for individuals over 40 years old (4/4). Conclusion: This mutation is located in a highly conserved amino acid region and is likely to be involved in protein oligomerisation by disulfide linked polymer formation. This important feature may be associated with the reduction in trabecular outflow and IOP elevation, and may justify the strong correlation between mutation and disease, and the early onset of glaucoma in this population.