title: Glaucoma phenotype in a large Swiss pedigree with the myocilin Gly367Arg mutation.
abstract: OBJECTIVE
  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 mm Hg, range 24-50 mm Hg; 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.
authors.affiliation: Department of Ophthalmology, University of Bern, Inselspital, Bern, Switzerland.
authors.forename: M E
authors.initials: ME
authors.lastname: Iliev
authors.forename: S
authors.initials: S
authors.lastname: Bodmer
authors.forename: S
authors.initials: S
authors.lastname: Gallati
authors.forename: R
authors.initials: R
authors.lastname: Lanz
authors.forename: J
authors.initials: J
authors.lastname: Sturmer
authors.forename: K
authors.initials: K
authors.lastname: Katsoulis
authors.forename: S
authors.initials: S
authors.lastname: Wolf
authors.forename: P
authors.initials: P
authors.lastname: Trittibach
authors.forename: G M
authors.initials: GM
authors.lastname: Sarra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D055815:Young Adult; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin