Penetrance and phenotype of the Cys433Arg myocilin mutation in a family pedigree with primary open-angle glaucoma.
OBJECTIVE
To evaluate the penetrance and the clinical characteristics of the Cys433Arg myocilin mutation in a family pedigree with primary open-angle glaucoma.


METHODS
Primary open-angle glaucoma was defined as untreated intraocular pressure (IOP) over 24 mmHg, with characteristic optic nerve and visual field glaucomatous damage. Patients with IOP <24 mm Hg who were currently being treated for primary open-angle glaucoma were included as affected individuals. Genomic DNA was collected from peripheral blood. PCR, single-strand conformation polymorphism, and sequencing analyses were performed to identify the presence of the Cys433Arg mutation in family members.


RESULTS
Of the 48 members of this family evaluated, 17 (35%) were found to harbor the Cys433Arg mutation, 9 (53%) of whom were glaucomatous. None of the 31 individuals without the mutation had glaucoma. Among the 9 patients with glaucoma, 5 had undergone surgical procedure to improve IOP control, including all patients older than 40 years of age. The mutation's penetrance was 0% in persons younger than 10 years (0/4), 40% in those 11 to 30 years (2/5), 75% in persons 30 to 40 years (3/4), and 100% in those older than 40 years (4/4).


CONCLUSIONS
The Cys433Arg mutation in this pedigree was associated with a phenotype characterized by early-onset open-angle glaucoma, which frequently requires surgical intervention and is associated with a high penetrance
de Vasconcellos
José Paulo Cabral
JP
Department of Ophthalmology, University of Campinas, Campinas, Brazil. cabraljp@uol.com.br
de Melo
Mônica Barbosa
MB
Schimiti
Rui
R
Costa
Fernando Ferreira
FF
Costa
Vital Paulino
VP
D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003545:Cysteine / Q000235:genetics; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D019683:Penetrance; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D000099179:Myocilin
D001120:Arginine; D003545:Cysteine; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin