ULOGA GENA MODIFIKATORA NA KLINIČKI TOK DIŠENOVE MIŠIĆNE DISTROFIJE
Sažetak
Dišenova mišićna distrofija je najčešća nasledna bolest mišića u dečjem uzrastu, koja ima progresivan klinički tok sa smrtnim ishodom koji najčešče nastaje u uzrastu od druge do četvrte decenije života. Bolest se nasleđuje X vezano, recesivno i u dve trećine pacijenta prenosi se preko majke, dok je u preostaloj trećini pacijenata u pitanju „de novo“ mutacija. Mutacije u genu za distrofin (DMD genu) tipa delecija, duplikacija i malih mutacija mogu se naći celom dužinom gena. Bolest počinje između treće i pete godine života, a inicijalne mišićne slabosti klinički se manifestuju kao sporije trčanje, otežano penjanje uz stepenice ili otežano ustajanje iz čučnja. Nekada, slučajno otkrivene, povišene vrednosti keratin kinaze ili usporeno usvajanje miljokaza ranog psihomotornog razvoja kod deteta sa hipertrofičnim listovima mogu pokrenuti dijagnostički postupak u pravcu Dišenove mišićne distrofije. Bolest najčešće ima uniforman klinički tok i podrazumeva vremenski jasan sled događaja. Mišićne slabosti vode ka gubitku hoda, potom i funkcije gornjih ekstremiteta, do potpune imobilnosti, uz pojavu dilatativne kardiomiopatije i respiratorne insuficijencije, koje su glavni uzrok smrtnog ishoda. Određeni pacijenti pokazuju odstupanja od navedenog u smislu duže funkcionalnosti i kasnijeg gubitka samostalnog hoda, kasnije nastale kardiomiopatije i respiratorne insuficijencije i vice versa. Smatra se da pored, primene savremenih mera nege i lečenja obolelih, uticaj na klinički tok imaju i geni nezavisni od kauzalnog DMD gena, koji utiču na procese u distrofičnom mišiću, pre svega na proces inflamacije, fibroze i masne infiltracije, preko specifičnih signalnih puteva. Do sada je opisano šest gena čije varijante modifikuju tok Dišenove mišićne distrofije. SPP1 (eng. secreted phosphoprotein 1) je prvi opisani gen čiji je G alel varijante rs28357094 udružen sa ranijim uzrastom gubitka hoda. Pored navedenog opisane su i varijante u genima: LTBP4 (eng. latent transforming growth factor-β binding protein 4), CD40, ACTN3 (eng. actinin 3), THBS1 (eng. thrombospondin 1) i TCTEX1D1 (eng. Tctex1 domain containing 1).
Cilj rada je predstavljanje do sada poznatih gena modifikatora Dišenove mišićne distrofije i njhovog uticaja na klinički tok bolesti.
Reference
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