Identifying inversions with Breakpoints in the Dystrophin Gene through Long-Read Sequencing: Report of Two Cases

Abstract Background: Duchenne Muscular Dystrophy (DMD) is an X-linked disorder caused by mutations in the DMD gene, with large deletions being the most frequent type of mutation. Large inversions involving the DMD gene are a less common cause of the disorder, primarily because they often elude detection by standard diagnostic methods such as multiplex ligation probe amplification (MLPA) and whole exome sequencing (WES) utilizing next-generation sequencing (NGS) technologies. Case presentation: Our research uncovered two intrachromosomal inversions involved the dystrophin gene in two unrelated families through Long-read sequencing (LRS). To confirm these variants, Sanger sequencing subsequently carried out. The first case involved a pericentric inversion from DMD intron 47 to the Xq27.3. The second case featured a paracentric inversion between DMD intron 42 and Xp21.1, inherited from the mother. In both cases, simple repeat sequences (SRS) were present at the breakpoints of these inversions. Conclusions: Our findings demonstrate that LRS can be effectively used to detect atypical mutation. The identification of SRS at breakpoints in DMD patients assists in acquiring a more profound understanding of the mechanisms involved in structural variations, thereby facilitating exploration into potential treatments.