Penetrance and Phenotype of the Cys433Arg Myocilin Mutation in a Family Pedigree with Primary Open-Angle Glaucoma

• Published in: Journal of glaucoma Vol. 12; no. 2; pp. 104 - 107
• Main Authors: de Vasconcellos, José Paulo Cabral, de Melo, Mônica Barbosa, Schimiti, Rui, Costa, Fernando Ferreira, Costa, Vital Paulino
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins, Inc 01-04-2003
• Subjects: Adolescent; Adult; Arginine - genetics; Child; Child, Preschool; Cysteine - genetics; Cytoskeletal Proteins; DNA Mutational Analysis; Eye Proteins - genetics; Female; Glaucoma, Open-Angle - diagnosis; Glaucoma, Open-Angle - genetics; Glaucoma, Open-Angle - surgery; Glycoproteins - genetics; Humans; Intraocular Pressure; Male; Middle Aged; Pedigree; Penetrance; Point Mutation; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational
• ISSN: 1057-0829; 1536-481X
• DOI: 10.1097/00061198-200304000-00003

PURPOSETo evaluate the penetrance and the clinical characteristics of the Cys433Arg myocilin mutation in a family pedigree with primary open-angle glaucoma.
PATIENTS AND METHODSPrimary 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.
RESULTSOf 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).
CONCLUSIONThe 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