Clinical features associated with mutations in the chromosome 1 open-angle glaucoma gene (GLC1A)
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.
Alward
W L
WL
Department of Ophthalmology, University of Iowa, Iowa City 52242, USA.
Fingert
J H
JH
Coote
M A
MA
Johnson
A T
AT
Lerner
S F
SF
Junqua
D
D
Durcan
F J
FJ
McCartney
P J
PJ
Mackey
D A
DA
Sheffield
V C
VC
Stone
E M
EM
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
D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin