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=12

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=<p><bold>Background:</bold> Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are two subtypes of muscular dystrophy diseases caused by pathogenic mutations in the <italic>DMD</italic> gene. Until now, more than 4,600 disease-causing mutations in <italic>DMD</italic> have been reported. However, only 33 mutations were deep intronic, cases with this type of mutations were limited.</p><p><bold>Methods:</bold> In this study, we used a combination of complementary DNA (cDNA) and target DNA sequencing analysis in addition to conventional whole-exome sequencing (WES).</p><p><bold>Results:</bold> Three novel hemizygous mutations IVS11 + 17811C &gt; G (c.1331 + 17811C &gt; G), IVS21 + 3252A &gt; G (c.2803 + 3252A &gt; G) and IVS40 + 362A &gt; G (c.5739 + 362A &gt; G) were identified in DMD patients, while a reported hemizygous mutation IVS62-285A &gt; G (c.9225-285A &gt; G) was found in the BMD patient. These <italic>DMD</italic> mutations lead to pseudoexon insertions, causing the generation of truncated and dysfunctional dystrophin.</p><p><bold>Conclusion:</bold> 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 <italic>DMD</italic> gene in which the mutational spectrum is complex.</p>