A novel deep intronic variant introduce dystrophin pseudoexon in Becker muscular dystrophy: A case report
Chang Liu,
Yanyu Lu,
Haiyan Yu,
Zhihao Xie,
Chengyue Sun,
Xinchao Cheng,
Fangfang Niu,
Yawen Zhao,
Jianwen Deng,
Lingchao Meng,
Zhaoxia Wang,
Yun Yuan,
Zhiying Xie
Affiliations
Chang Liu
Department of Neurology, Peking University First Hospital, Beijing, 100034, China
Yanyu Lu
Department of Neurology, Peking University First Hospital, Beijing, 100034, China
Haiyan Yu
Department of Clinical Laboratory, Peking University First Hospital, Beijing, 100034, China
Zhihao Xie
Department of Epidemiology and Biostatistics, West China School of Public Health, Sichuan University, Chengdu, 610041, China
Chengyue Sun
Department of Neurology, Peking University People's Hospital, Beijing, 100044, China
Xinchao Cheng
Department of Bioinformatics, Berry Genomics, Beijing, 102206, China
Fangfang Niu
Department of Bioinformatics, Berry Genomics, Beijing, 102206, China
Yawen Zhao
Department of Neurology, Peking University First Hospital, Beijing, 100034, China
Jianwen Deng
Department of Neurology, Peking University First Hospital, Beijing, 100034, China
Lingchao Meng
Department of Neurology, Peking University First Hospital, Beijing, 100034, China
Zhaoxia Wang
Department of Neurology, Peking University First Hospital, Beijing, 100034, China
Yun Yuan
Department of Neurology, Peking University First Hospital, Beijing, 100034, China; Corresponding author.
Zhiying Xie
Department of Neurology, Peking University First Hospital, Beijing, 100034, China; Corresponding author. Department of Neurology, Peking University First Hospital, #8 Xishiku Street, Xicheng District, Beijing, 100034, China.
Most pathogenic DMD variants are detectable and interpretable by standard genetic testing for dystrophinopthies. However, approximately 1∼3% of dystrophinopthies patients still do not have a detectable DMD variant after standard genetic testing, most likely due to structural chromosome rearrangements and/or deep intronic pseudoexon-activating variants. Here, we report on a boy with a suspected diagnosis of Becker muscular dystrophy (BMD) who remained without a detectable DMD variant after exonic DNA-based standard genetic testing. Dystrophin mRNA studies and genomic Sanger sequencing were performed in the boy, followed by in silico splicing analyses. We successfully detected a novel deep intronic disease-causing variant in the DMD gene (c.2380 + 3317A > T), which consequently resulting in a new dystrophin pseudoexon activation through the enhancement of a cryptic donor splice site. The patient was therefore genetically diagnosed with BMD. Our case report further emphasizes the significant role of disease-causing splicing variants within deep intronic regions in genetically undiagnosed dystrophinopathies.
