Clinical features associated with mutations in the chromosome 1 open-angle glaucoma gene (GLCIA)

Background A substantial proportion of cases of glaucoma have a genetic basis, Mutations causing glaucoma have been identified in the chromosome 1 open-angle glaucoma gene (GLC1A), which encodes a 57-kd protein known as myocilin. The normal role of this protein and the mechanism by which mutations cause glaucoma are not known, Methods We screened 716 patients with primary open-angle glaucoma and 596 control subjects For sequence changes in the GLC1A gene. Results We identified 16 sequence variations that met the criteria for a probable disease-causing mutation because they altered the predicted amino acid sequence and they were found in one or more patients with glaucoma and in less than 1 percent of the control subjects. These 16 mutations were found in 33 patients (4.6 percent). Six of the mutations were found in more than 1 subject: (total, 99). Clinical features associated with these six mutations included an age at diagnosis ranging from 8 to 77 years and maximal recorded intraocular pressures ranging from 12 to 77 mm Hg, Conclusions A variety of mutations in the GLC1A gene are associated with glaucoma, The spectrum of disease can range from juvenile glaucoma to typical late-onset primary open-angle glaucoma. (C) 1998, Massachusetts Medical Society.