第十一届北京罕见病学术大会暨2023京津冀罕见病学术大会征文(085)

1Department of Neurology， Peking University First Hospital

2Department of Clinical Laboratory， Peking University First Hospital，

3Department of Epidemiology and Biostatistics， West China School of Public Health and West China Fourth Hospital， Sichuan University

4Department of Neurology， Peking University People＇s Hospital，

5Department of Cardiology， Peking University people’s Hospital，

Chang Liu^1†， Yanyu Lu^1†， Haiyan Yu²， Zhihao Xie³， Chengyue Sun⁴， Shu Fang⁵，

Chen Ling¹， Yawen Zhao¹， Yiming Zheng¹， Jianwen Deng¹， Lingchao Meng¹，

Zhaoxia Wang¹， Yun Yuan^1*， Zhiying Xie^1†

Most pathogenic DMD variants are detectable by standard genetic testing for dystrophinopthies. However， approximately 1~3% of dystrophinopthies patients remain without a pathogenic DMD variant after standard testing， most likely due to deep intronic variants. We report on a boy with a suspected diagnosis of Becker muscular dystrophy (BMD) based on his clinical and pathological characteristics， who remained genetically unsolved after standard testing. We performed muscle-derived DMD mRNA studies of the patient， followed by genomic Sanger sequencing and in silico splicing analyses. We successfully detected a novel deep intronic DMD variant， the c.2380+3317A>T variant， which resulted in a new pseudoexon activation through the enhancement of a cryptic donor splice site. Hence， the patient was genetically diagnosed with BMD. Our case report emphasizes the significant role of deep-intronic pseudoexon-activating variants in genetically unsolved dystrophinopathies.