title: [Study of TIGR gene in patients with primary open angle glaucoma].
abstract: OBJECTIVE
  The aim of the study was to identify the mutations of TIGR gene in Polish patients with primary open angle glaucoma (POAG), and to define the genotype-phenotype correlation, between the type of mutation and the clinical picture of POAG.
  
  
  METHODS
  The study included 45 patients with verified and proved diagnosis of POAG. DNA was isolated from peripheral blood lymphocytes of patients. The PCR amplification of all three exons of TIGR gene was done for every patient. The screening for the sequence changes in the PCR products of TIGR gene was done using conformation sensitive gel electrophoresis (CSGE). The probes with identified heteroduplexes were sequenced using an automatic DNA sequencer.
  
  
  RESULTS
  During amplification of the coding regions of TIGR gene and the promoter sequences and flanking sequences of introns, 315 PCR products were obtained. The CSGE analysis of these PCR products allowed to detect 60 possible changes of sequence in 28 patients. 34 heteroduplexes were chosen for sequencing, including 29 unique changes and 5 changes representative for repeated, identical heteroduplexes. Direct sequencing allowed to detect only four different changes in TIGR gene sequence. Three of them: 5'UTR -83G-->A (present in 14 patients), +227 exon 1 G-->A, Arg76Lys (present in 14 patient) and +311 exon 3 T-->C, Tyr347Tyr (present in 4 patients) were already described in literature as neutral polymorphisms of TIGR gene. Only one change in promoter: 5'UTR 126T-->C (present in 2 patients) was not described in the literature to date. However, because this change doesn't alter directly the sequence of aminoacids in protein product of TIGR gene, it is very difficult to conclude its pathogenetic role.
  
  
  CONCLUSIONS
  Our studies have shown no TIGR gene changes that can be recognized as causative mutations in development of POAG. Thus, the definition of any genotype-phenotype correlation was impossible. The study on the role of the change in promoter sequence that was not yet described, will be continued. Exclusion of TIGR gene mutations in Polish patients with POAG means that they probably have mutations in other genes, what paves the way to the studies on other loci that predispose to POAG.
authors.affiliation: Z Katedry i Zakładu Genetyki Medycznej Akademii Medycznej w Poznaniu.
authors.forename: Maciej R
authors.initials: MR
authors.lastname: Krawczyński
authors.forename: Malwina
authors.initials: M
authors.lastname: Czarny-Ratajczak
authors.forename: Krystyna
authors.initials: K
authors.lastname: Pecold
authors.forename: Anna
authors.initials: A
authors.lastname: Latos-Bieleńska
mesh_terms: D003598:Cytoskeletal Proteins; D004247:DNA / Q000097:blood; D053938:DNA Fragmentation / Q000235:genetics; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D016521:Electrophoresis, Gel, Pulsed-Field; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D012720:Severity of Illness Index; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D004247:DNA; D017931:DNA Primers; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin