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