Genetic screening in a large family with juvenile onset primary open angleglaucoma

Aims-A number of genetic loci have been implicated in the pathogenesis of p rimary open angle glaucoma (POAG). The aim of this study was to identify th e 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. Bas e excision sequence scanning was carried out in order to test for the prese nce 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. Conclusios-The Gly252Arg mutation in the TIGR gene results in the developme nt of POAG in this family. It was possible to identify younger, currently u naffected, members of the family who carry the mutation and who are therefo re at a very high risk of developing POAG themselves. This is the first dem onstration that Gly252Arg can be a disease causing mutation rather than a b enign polymorphism. The possible pathogenic mechanisms and wider implicatio ns of the mutation are considered.