title: Clinical features associated with mutations in the chromosome 1 open-angle glaucoma gene (GLC1A)
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.
authors.affiliation: Department of Ophthalmology, University of Iowa, Iowa City 52242, USA.
authors.forename: W L
authors.initials: WL
authors.lastname: Alward
authors.forename: J H
authors.initials: JH
authors.lastname: Fingert
authors.forename: M A
authors.initials: MA
authors.lastname: Coote
authors.forename: A T
authors.initials: AT
authors.lastname: Johnson
authors.forename: S F
authors.initials: SF
authors.lastname: Lerner
authors.forename: D
authors.initials: D
authors.lastname: Junqua
authors.forename: F J
authors.initials: FJ
authors.lastname: Durcan
authors.forename: P J
authors.initials: PJ
authors.lastname: McCartney
authors.forename: D A
authors.initials: DA
authors.lastname: Mackey
authors.forename: V C
authors.initials: VC
authors.lastname: Sheffield
authors.forename: E M
authors.initials: EM
authors.lastname: Stone
mesh_terms: D017668:Age of Onset; D000368:Aged; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1; D003598:Cytoskeletal Proteins; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D009154:Mutation; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin