Mutations in the myocilin (MYOC) gene are responsible for 3 to 5% of primary open angle glaucoma, thus predictive DNA testing in family members of some glaucoma pedigrees is possible.
Arg46Stop occurred with similar frequency in patients with POAG and control subjects, suggesting that the reduced amount of TIGR/MYOC predicted to result from this truncation does not dramatically increase or decrease risk of glaucoma.
To explore the biological role of myocilin and the pathogenesis of glaucoma, we have analyzed the expression of recombinant wild type and four representative pathogenic myocilin mutations (E323K, Q368X, P370L, and D380A) in transiently transfected cell lines derived from ocular and nonocular tissues.
The lack of clinical evidence of glaucoma suggests that haploinsufficiency of the TIGR/MYOC protein is not the cause of early-onset glaucoma associated with mutations in TIGR/MYOC.
Positive family history is an important risk factor and previous studies indicate that approximately 5% of POAG results from mutations in the myocilin ( MYOC) gene, raising the possibility of identifying individuals genetically predisposed to glaucoma.
Ninety-one Chinese patients with POAG and 113 of their family members without glaucoma were screened for sequence alterations in the TIGR gene by polymerase chain reaction, conformation-sensitive gel electrophoresis, and DNA sequencing.
Neither the individual homozygous for the Gln368STOPmyocilin mutation nor her younger heterozygous siblings displayed any signs suggestive of glaucoma.
The finding that a TIGR/MYOC mt.1(+) determination provided a strong marker for glaucoma progression, above and beyond the other baseline risk factors, suggests a clinical utility in testing for this promoter genotype.
Surprisingly, mice expressing Tyr423His mutant myocilin, corresponding to a severe glaucoma-causing mutation (Tyr437His) in human subjects, exhibit a weak, if any, glaucoma phenotype.
Predictive genetic testing of relatives of known myocilin (MYOC) gene mutation carriers is an appropriate strategy to identify individuals at risk for glaucoma.
Our present findings, along with the absence of glaucoma in mice completely lacking MYOC, show that changing the level of MYOC is not pathogenic (from absent to approximately 15 times normal).
The pathogenesis of glaucoma associated with GLC1A gene mutations might be more complex than expected, and (unknown) suppressor mechanisms have to be considered.
The aim of this study was to characterize a representative sample of the Peruvian population suffering open-angle glaucoma (OAG) with respect to the myocilin gene (MYOC) mutations, glaucoma phenotype, and ancestry for future glaucoma risk assessment.