AUTHOR=Xie Zhiying , Liu Chang , Lu Yanyu , Sun Chengyue , Liu Yilin , Yu Meng , Shu Junlong , Meng Lingchao , Deng Jianwen , Zhang Wei , Wang Zhaoxia , Lv He , Yuan Yun 

TITLE=Exonization of a deep intronic long interspersed nuclear element in Becker muscular dystrophy

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.979732

DOI=10.3389/fgene.2022.979732

ISSN=1664-8021

ABSTRACT=<p>The precise identification of pathogenic <italic>DMD</italic> variants is sometimes rather difficult, mainly due to complex structural variants (SVs) and deep intronic splice-altering variants. We performed genomic long-read whole <italic>DMD</italic> gene sequencing in a boy with asymptomatic hyper-creatine kinase-emia who remained genetically undiagnosed after standard genetic testing, dystrophin protein and <italic>DMD</italic> mRNA studies, and genomic short-read whole <italic>DMD</italic> gene sequencing. We successfully identified a novel pathogenic SV in <italic>DMD</italic> intron 1 <italic>via</italic> long-read sequencing. The deep intronic SV consists of a long interspersed nuclear element-1 (LINE-1) insertion/non-tandem duplication rearrangement causing partial exonization of the LINE-1, establishing a genetic diagnosis of Becker muscular dystrophy. Our study expands the genetic spectrum of dystrophinopathies and highlights the significant role of disease-causing LINE-1 insertions in monogenic diseases.</p>