Analysis of complex structural variants in the DMD gene in one family

This work describes a family with Duchenne muscular dystrophy (DMD) rare case of symptomatic pregnant woman. The main aim was to perform prenatal molecular diagnosis provide genetic counseling. secondary suggest the mechanisms causing complex structural variant (cxSV) identified. To accomplish this, we used multi-technique algorithm including segregation analysis, Multiplex Ligation-dependent Probe Amplification, PCR, X-chromosome inactivation studies, microarrays, whole genome sequencing and bioinformatics. We identified duplication exons 38–43 in DMD gene all affected obligate carrier members, proving that this DMD-causing mutation. also observed skewed woman explained her symptomatology. In addition, cxSV (duplication deletion 45–54) boy. characterization bioinformatic analyses breakpoint junctions allowed us identify Double Strand Breaks stimulator motifs suggested replication-dependent Fork Stalling Template Switching as most probable leading duplication. de novo might have been result germline inter-chromosome non-allelic recombination involving Non-Homologous End Joining mechanism. conclusion, diagnostic strategy accurate familial together in-depth helped determine chronology events, propose understand involved generation rearrangement.