Clinical features associated with mutations in the chromosome 1 open-angle glaucoma gene (GLC1A)

N Engl J Med. 1998 Apr 9;338(15):1022-7. doi: 10.1056/NEJM199804093381503.

Abstract

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, 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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age of Onset
  • Aged
  • Case-Control Studies
  • Chromosomes, Human, Pair 1*
  • Cytoskeletal Proteins
  • Eye Proteins / genetics*
  • Female
  • Glaucoma, Open-Angle / genetics*
  • Glycoproteins / genetics*
  • Humans
  • Lod Score
  • Male
  • Mutation*

Substances

  • Cytoskeletal Proteins
  • Eye Proteins
  • Glycoproteins
  • trabecular meshwork-induced glucocorticoid response protein