Zbornik - Društvo genetičara Srbije

222 ZBORNIK ABSTRAKATA III KONGRESA GENETIÈARA SRBIJE V-Pos-19
Subotica, 30. novembar - 4. decembar 2004.
MOGUÆNOSTI MOLEKULARNE DIJAGNOSTIKE HEREDITARNE
HEMOHROMATOZE TIP1 U SRBIJI I CRNOJ GORI
Lj. Zamuroviæ 1 ,M.Šariæ 1 , M. Keckareviæ-Markoviæ 1 , B. Èuljkoviæ 1 ,J.Joviæ 2 ,S.Romac 1
1 Biološki fakultet Univerziteta u Beogradu
2 Vojnomedicinska akademija, Beograd
Hereditarna hemohromatoza (HH) je èest, genetski uzrokovan poremeæaj metabolizma
gvoða. Nasleðuje se autozomalno recesivno. Najèešæi tip bolesti, HH tip1, je posledica
mutacije u HFE genu (6p21.3). Do sada su opisane 3 missense mutacije: tranzicija G u A
na poziciji 845 HFE gena (C282Y), transverzija C u G na poziciji 187 (H63D) i
transverzija A u T na 193 poziciji (S65C). U 83% sluèajeva oboleli su homozigoti za
C282Y mutaciju. Druge dve mutacije se kod pacijenata javljaju znatno reðe, uglavnom u
obliku kombinovanih heterozigota sa prvom mutacijom (C282Y/H63D i C282Y/S65C).
U našoj laboratoriji uspostavljena je molekularna dijagnostika HH bazirana na umnoavanju
eljenog regiona HFE gena PCR metodom, restrikcionom digestijom PCR
produkata i njihovom analizom na 3% agaroznom i 6% denaturišuæem poliakrilamidnom
gelu.
Znaèaj uvoðenja ove analize je u obezbeðivanju dopunske dijagnostièke metode koja
poveæava pouzdanost dijagnostike, olakšava dijagnostiku u ranim fazama bolesti, kada
se adekvatnim leèenjem mogu izbeæi ireverzibilna ošteæenja organa, kao i u otkrivanju
grupa sa poveæanim rizikom od oboljevanja. Pored toga, analiza HFE gena moe dati
znaèajne podatke o uèestalosti mutacija u ovom genu u populaciji SCG.
POSSIBILITIES OF MOLECULAR DIAGNOSTIC OF HEREDITARY
HEMOCHROMATOSIS TYPE1 IN SERBIA AND MONTENEGRO
Hereditary hemochromatosis is a common, autosomal recessive genetic disorder of iron
metabolism. The most common form (HH type1) is caused by the mutations in HFE gene
(6p21.3). Three missense mutations have been described so far: transition G to A at position
845 of HFE gene (C282Y), transversion C to G at position 187 (H63D) and
transversion at position 193 (S65C). 83% of patients are homozygous for the C282Y mutation.
The other two mutations are less common and mostly in form of compound
heterozygots with the first mutation in phenotypic HH patients.
In our laboratory, molecular diagnostic of HH has been established, based on amplification
of the selected region of HFE by PCR, restriction enzyme digest and analisys on 3%
agarose and 6% denaturing polyacrilamid gel.
The importance of its application is in developing an additional diagnostic method which
increases the liability of diagnosis, provide diagnosis in the early phases of illness, when
is possible with appropriate treatment to avoid irreversible organ damage, and is also
helpful as a screening to identify high-risc group. In addition, the HFE gene analysis can
provide important data about prevalence of mutations in this gene in the population of
Serbia and Montenegro.