Abstrakt

Anemia Fanconiego (FA) jest rzadką chorobą genetyczną wywołaną mutacjami w genach, których produkty białkowe zaangażowane są w ważne procesy zachodzące w komórce, takie jak: replikacja, kontrola cyklu komórkowego oraz naprawa uszkodzeń DNA. Charakteryzuje się: wadami wrodzonymi, niewydolnością szpiku oraz zwiększoną predyspozycją do nowotworów. Objawy fenotypowe, obecne u około 75% chorych, najczęściej obejmują nieprawidłowości: niskorosłość, małogłowie, wady kciuka i promieniowej strony kończyn górnych, zaburzenia pigmentacji skóry, wady układu pokarmowego i moczowo-płciowego. Postępująca niewydolność szpiku pojawia się w pierwszej dekadzie życia, często początkowo z leukopenią lub małopłytkowością. Najczęstszymi nowotworami występującymi u chorych z FA są: zespoły mielodysplastyczne (MDS) i ostra białaczka szpikowa oraz guzy lite głowy i szyi, skóry, przewodu pokarmowego i układu moczowo-płciowego. Dotychczas zidentyfikowano 22 geny anemii Fanconiego (FANC). Ich loci znajdują się na chromosomach autosomalnych, poza FANCB umiejscowionym na chromosomie X. Produkty białkowe tych genów biorą udział w ścieżce zwanej szlakiem anemii Fanconiego, która reguluje działanie systemów naprawy uszkodzeń DNA. Diagnostykę anemii Fanconiego rozpoczyna się od badania różnicującego zespoły niestabilności chromosomowej – testu z mitomycyną C (MMC) lub z diepoksybutanem (DEB), w których u chorych z anemią Fanconiego obserwuje się liczne złamania i pęknięcia chromosomów oraz charakterystyczne figury promieniste. W celu wykrycia mutacji leżącej u podłoża anemii Fanconiego stosuje się metody molekularne. Badaniem z wyboru jest analiza DNA metodą sekwencjonowania następnej generacji (NGS).

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