Novel Intronic Mutations Introduce Pseudoexons in DMD That Cause Muscular Dystrophy in Patients.

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are two subtypes of muscular dystrophy diseases caused by pathogenic mutations in the gene. Until now, more than 4,600 disease-causing mutations in have been reported. However, only 33 mutations were deep intronic, cases with this type of mutations were limited. In this study, we used a combination of complementary DNA (cDNA) and target DNA sequencing analysis in addition to conventional whole-exome sequencing (WES). Three novel hemizygous mutations IVS11 + 17811C > G (c.1331 + 17811C > G), IVS21 + 3252A > G (c.2803 + 3252A > G) and IVS40 + 362A > G (c.5739 + 362A > G) were identified in DMD patients, while a reported hemizygous mutation IVS62-285A > G (c.9225-285A > G) was found in the BMD patient. These mutations lead to pseudoexon insertions, causing the generation of truncated and dysfunctional dystrophin. This study defines three novel and one reported intronic mutations, which can result in DMD/BMD. We also emphasize the need to combine WES and cDNA-based methods to detect the variant in the very large gene in which the mutational spectrum is complex.