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Abstract #21731 Published in IGR 10-3
Glaucoma phenotype in a large Swiss pedigree with the myocilin Gly367Arg mutation
Iliev ME; Bodmer S; Gallati S; Lanz R; Sturmer J; Katsoulis K; Wolf S; Trittibach P; Sarra GMEye 2008; 22: 880-888
AIMS: To characterize genotype, phenotype, and age-related penetrance in a Swiss pedigree with juvenile open-angle glaucoma (JOAG). METHODS: In a large Swiss family with history of glaucoma and 82 living members of four generations, we conducted molecular analysis and a detailed phenotype characterization in 52 family members. Mutation analysis was carried out using single-strand conformation polymorphism and DNA sequence analyses of the suspected candidate gene, myocilin (MYOC). RESULTS: We detected a Gly367Arg mutation in the MYOC gene of 13 family members. Nine of them (69.2%) had glaucoma: mean IOP 35.3 mmHg, range 24-50 mmHg; mean age at diagnosis 34.9 years, range 28-51 years. Two mutation carriers were glaucoma suspects, one (age 15) was unaffected, and one (age 16) not available for clinical examinations. Age-related glaucoma penetrance was 50% at 30 and 78% at 40. Untreated IOP resulted in rapid disease progression, whereas good IOP control, usually only by means of filtration surgery, could stabilize the disease. None of the wild-type members had glaucoma. CONCLUSIONS: This Swiss family is the largest reported Gly367Arg pedigree to date. The exact genotype and phenotype characterization allowed a reliable risk and prognosis assessment and targeted eye-care planning for the family. The study demonstrates the importance of genetic investigations in glaucoma families, carrying the potential of long-term socio-economic benefits.
Dr. M.E. Iliev, Department of Ophthalmology, University of Bern, Inselspital, Bern, Switzerland
Classification:
1.2 Population genetics (Part of: 1 General aspects)
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)