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NR 4-5/2004
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Badania genu TIGR u
pacjentów z pierwotną jaskrą otwartego kąta
Study of TIGR gene in
patients with primary open angle glaucoma
Maciej R. Krawczyński, Malwina
Czarny-Ratajczak, Krystyna Pecold1, Anna
Latos-Bieleńska
Z Katedry i Zakładu Genetyki Medycznej Akademii Medycznej w
Poznaniu
Kierownik: prof. dr hab. n. med. Anna Latos-Bieleńska
1Z Katedry i Kliniki Okulistyki Akademii Medycznej w
Poznaniu
Kierownik: prof. dr hab. n. med. Krystyna Pecold |
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| Summary: |
Purpose: 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.
Material and 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. |
| Słowa kluczowe: |
jaskra pierwotna otwartego
kąta, genetyka, gen TIGR. |
| Key words: |
primary open angle
glaucoma, genetics, TIGR gene. |
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