AUTHOR=Lu Xinguo , Han Chunxi , Mai Jiahui , Jiang Xianping , Liao Jianxiang , Hou Yanqi , Cui Di 

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

JOURNAL=Frontiers in Genetics

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.657040

DOI=10.3389/fgene.2021.657040

ISSN=1664-8021

ABSTRACT=Background: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are two subtypes of muscular dystrophy diseases caused by pathogenic mutations in the DMD gene. Until now, more than 4,600 disease-causing mutations in DMD have been reported. However, only 33 mutations were deep intronic, cases with this type of mutations were limited. 
Methods: In this study, we used a combination of complementary DNA (cDNA) and target DNA sequencing analysis in addition to conventional whole-exome sequencing (WES). 
Results: 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 DMD mutations lead to pseudoexon insertions, causing the generation of truncated and dysfunctional dystrophin. Conclusion: 
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 DMD gene in which the mutational spectrum is complex.