title: Genetic screening in a large family with juvenile onset primary open angle glaucoma.
abstract: OBJECTIVE
  A number of genetic loci have been implicated in the pathogenesis of primary open angle glaucoma (POAG). The aim of this study was to identify the genetic cause of POAG in a large Scottish family and, if possible, offer genetic screening and advice to family members.
  
  
  METHODS
  Family members were examined to determine their disease status. Base excision sequence scanning was carried out in order to test for the presence of a POAG causing mutation at known genetic loci. Direct DNA sequencing was performed in order to determine the mutation sequence.
  
  
  RESULTS
  All family members of known affected disease status and two family members of unknown disease status were found to have a mutation in the TIGR gene. The mutation resulted in the substitution of a glycine residue with an arginine residue at codon 252 (Gly252Arg). No other sequence variations were present in any members of the family.
  
  
  CONCLUSIONS
  The Gly252Arg mutation in the TIGR gene results in the development of POAG in this family. It was possible to identify younger, currently unaffected, members of the family who carry the mutation and who are therefore at a very high risk of developing POAG themselves. This is the first demonstration that Gly252Arg can be a disease causing mutation rather than a benign polymorphism. The possible pathogenic mechanisms and wider implications of the mutation are considered.
authors.affiliation: Molecular Medicine Unit, University of Leeds. Paget.Booth@aol.com
authors.forename: A P
authors.initials: AP
authors.lastname: Booth
authors.forename: R
authors.initials: R
authors.lastname: Anwar
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: A J
authors.initials: AJ
authors.lastname: Churchill
authors.forename: J
authors.initials: J
authors.lastname: Jay
authors.forename: J
authors.initials: J
authors.lastname: Polansky
authors.forename: T
authors.initials: T
authors.lastname: Nguyen
authors.forename: A F
authors.initials: AF
authors.lastname: Markham
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D005820:Genetic Testing / Q000379:methods*; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA