Uporedna analiza duplikacija i delecija u genu za distrofin u grupi bolesnika sa distrofinopatijom iz Srbije

  • Jasmina Maksić VMA, Beograd, Kl. za Neurohirurgiju
  • Valerija Dobričić Neurology Clinic, Clinical Center of Serbia, Belgrade, Serbia
  • Lukas Rasulić Neurology Clinic, Clinical Center of Serbia, Belgrade, SerbiaFaculty of Medicine, University of Belgrade, Serbia
  • Nela Maksimović Faculty of Medicine, University of Belgrade, Serbia
  • Marija Branković Faculty of Medicine, University of Belgrade, Serbia
  • Vedrana Milić Rašić Clinic for Neurology and Psychiatry for Child and Youth, Clinical Center of Serbia, Belgrade, SerbiaFaculty of Medicine, University of Belgrade, Serbia
  • Vidosava Rakočević Stojanović Neurology Clinic, Clinical Center of Serbia, Belgrade, SerbiaFaculty of Medicine, University of Belgrade, Serbia
  • Ivana Novaković Faculty of Medicine, University of Belgrade, Serbia
DOI: https://doi.org/10.2298/VSP180226089M
Ključne reči: geni, delecija;, geni, duplikacija;, genetika, medicinska;, genetičke bolesti, urođene;, distrofija, mišićna, dišen;, žene

Sažetak


Uvod/Cilj. Dišenova mišićna distrofija (DMD) i njegova alelna forma, Bekerova mišićna distrofija (BMD), su X-vezane nasledne bolesti od kojih obolevaju muškarci, a karakteriše ih progresivna mišićna i kardiopulmonalna slabost, posebno kod DMD kao težeg oblika bolesti. Ove bolesti nastaju kao posledica mutacija u genu za distrofin, a najčešće su prisutne intragenske delecije i duplikacije (80%). Novonastalu mutaciju ima1/3 bolesnika, a procenjeno je da su 2/3 majki nosioci. Cilj rada je bio da se analizira uče­stalost duplikacija u odnosu na delecije u genu za distrofin kod bolesnika sa distrofinopatijom, kao i da se ispita efekat dobijenih mutacija na fenotip kod probanda i utvrdimo status nosioca kod ženskih srodnika probanda sa duplika­cijama. Metode. Studijom je bilo obuhvaćeno 22 DMD i 35 BMD nesrodnih bolesnika i šest ženskih srodnika probanda kod kojih su bile otkrivene duplikacije. Za otkrivanje ili pot­vrdu mutacije, kod probanda i ženskih nosioca, korišćene su metode: lančana reakcija polimerazom (PCR) i višestruko umnožavanje vezanih sondi (MLPA), prema datom pro­tokolu. Rezultati. Kod probanda je nađeno 34 (59,6%) velikih delecija (najčešće su bili zahvaćeni egzoni 44–60) i 6 velikih duplikacija (10,5%) kod 4 DMD i 2 BMD bolesnika. Takođe, duplikacije su nađene kod 3 od 4 (75%) testirane majke. Distribucija duplikacija je bila heterogena, obuhvatala je N-terminalni i štapićasti region i uključivala je veći broj egzona, osim kod jednog DMD bolesnika koji je imao du­plikaciju egzona 2. Odstupanje od Monakovog pravila je bilo prisutno kod 9,5% DMD probanda, odnosno kod 15,8% BMD probanda, to jest   kod 12,5% slučajeva. Zaključak. Kod 57 DMD/BMD probanda nađeno je 59,6% velikih delecija i 10,5% velikih duplikacija. Najčešće je bio zahvaćen štapićasti domen u DMD genu. Odstupanje od Monakovog pravila je bilo prisutno u 12,5% DMD/BMD slučajeva. Tri od četiri ispitane majke probanda su bile potvrđene kao nosioci.

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