The genetics of open-angle glaucoma: the story of GLC1A and myocilin.

A linkage analysis study was performed on a single large family with juvenile-onset primary open-angle glaucoma (POAG). This led to the recognition that there was a region of chromosome 1q that harboured a gene for juvenile-onset POAG. This chromosomal site was called GLC1A. It was discovered that a gene that produces the protein myocilin resides within this interval and that mutations in myocilin caused most cases of autosomal dominant juvenile-onset POAG. More importantly myocilin mutations also cause up to 4.6% of cases of adult-onset POAG. The prevalence of myocilin mutations is similar regardless of race or geographic location. There are widely variable glaucoma phenotypes depending on the specific mutation in myocilin. Myocilin is expressed in multiple tissues throughout the eye and in many other organs. In the trabecular meshwork the production of myocilin can be induced by the application of topical corticosteroids. The exact function of myocilin in health and disease remains a mystery.