Analysis of duplications versus deletions in the dystrophin gene in Serbian cohort with dystrophinopathies

  • Jasmina Maksić Faculty for Special Education and Rehabilitation, University of Belgrade, Serbia
  • 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
Keywords: gene deletion;, gene duplication;, genetics, medical;, genetic diseases, inborn;, muscular dystrophy, duchenne;, women

Abstract


Background/Aim. Duchenne muscular dystrophy (DMD) and its allelic form Becker muscular dystrophy (BMD) are X-linked diseases that affect males, characterized by pro­gressive muscle and cardiopulmonary weakness, especially in DMD as a severe form of the disease. They result from mutations in the dystrophin gene, and the most common changes are large intragenic deletions and duplications (80%). One third of patients have de novo mutation and 2/3 of the mothers are estimated as carriers. The aim of the study was to analyze the frequency of duplications versus deletions in the dystrophin gene in patients with dystro­phinopathies, as well as to analyze the phenotypic effect of large mutations obtained and to determine the carrier status of female relatives in probands with duplications. Methods. We examined 22 DMD and 35 BMD unrelated patients and 6 female relatives of the probands where duplications were found. We used polymerase chain reaction (PCR) and multi­plex ligation-dependent probe amplification (MLPA) met­hods, according to the protocol, to detect or confirm mu­ta­tions in probands and female carriers. Results. In probands, there were 34 (59.6%) large deletions (mostly affected exons 44–60) and 6 (10.5%) large duplications in 4 DMD and 2 BMD patients. Also, duplications were found in 3 out of 4 (75%) tested mothers. The distribution of duplications was heterogeneous, affecting N-terminal and central rod domain, and included more exons, except for one DMD patient who had duplication of exon 2. An exception from the Monaco rule was present in 9.5% of DMD and 15.8% of BMD probands, i.e. in 12.5% of DMD/BMD cases. Conclusion. In 57 DMD/BMD probands, we found 59.6% of large deletions and 10.5% of large duplications. The most affected region of the DMD gene was the central rod do­main. An exception to Monaco's rule was present in 12.5% of DMD/BMD cases. Three out of 4 examined proband's mothers were confirmed as carriers.

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Published
2021/05/21
Section
Original Paper