title: Only neutral polymorphisms found in the TIGR/myocilin gene of 45 Polish patients with primary open-angle glaucoma.
abstract: The aim of the study was to identify mutations of the TIGR gene in Polish patients with primary open-angle glaucoma (POAG) and to define possible genotype-phenotype correlations. The study included 45 patients with a verified diagnosis of POAG. The PCR amplification of all three exons of the TIGR gene and screening for the sequence changes by CSGE analysis was done for every patient. The probes with identified heteroduplexes were sequenced. Altogether 315 PCR products were obtained. The CSGE analysis detected 60 possible changes of the sequence in 28 patients. 34 heteroduplexes were chosen for sequencing, including 29 unique changes and 5 changes representative of identical heteroduplexes. Direct sequencing enabled detection of only four different changes in the TIGR gene sequence. Three of them: 5'UTR -83G-->A (in 14 patients), +227 exon 1 G-->A, Arg76Lys (in 14 patients) and +311 exon 3 T-->C, Tyr347Tyr (in 4 patients) have already been described in the literature as neutral polymorphisms of the gene. Only one change in the promoter, 5'UTR -126T-->C (in 2 patients), has not been described in the literature to date. However, this change does not alter directly the sequence of amino acids in myocilin, so it is difficult to conclude on its pathogenetic role. Thus our study showed only neutral polymorphisms of the TIGR gene. This suggests that the patients probably have mutations in other genes, so other loci that predispose to POAG must be analyzed.
authors.affiliation: Chair and Department of Medical Genetics, Karol Marcinkowski University of Medical Sciences, Poznań, Poland. mrkrawcz@amp.edu.pl
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; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005901:Glaucoma / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D016350:Leucine Zippers; D008297:Male; D011044:Poland; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D014129:Trabecular Meshwork; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin