A novel partial mRNA-derived duplication of the DMD gene identified in NGS carrier screening.

Duplications in the dystrophin gene (DMD) represent a common genetic variation associated with the onset of Duchenne and Becker muscular dystrophy. In this study, we reported a novel mRNA-derived DMD duplication identified by next-generation sequencing (NGS)-based expanded carrier screening (ECS) in a pregnant woman, which was not accurately detected by multiplex ligation probe amplification (MLPA) testing. The discrepancy was elucidated through the analysis of the duplication breakpoint via additional validation experiments. This variation was confirmed to originate from a partially reverse-transcribed intronless cDNA copy of a rare DMD gene transcript mRNA and reinserted into a noncoding region of chromosome 13. The variation was classified as benign because the DMD gene remained intact. We strongly recommend analysing the breakpoints before the pathogenicity assessment of DMD duplication variations, identified in ECS to improve the accuracy of clinical prediction and genetic counselling.