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(031)

1Department of Neurology， Peking University First Hospital，

2Department of Neurology， Peking University People＇s Hospital

3Department of Neurology， Beijing Tiantan Hospital， Capital Medical University

4Department of Neurology， Shandong Provincial Hospital Affiliated to Shandong First Medical University

5Department of Neurology， The First Affiliated Hospital of Zhengzhou University

Zhiying Xie^1†， Chengyue Sun^2†， Chang Liu¹， Yanyu Lu¹，

Bin Chen³， Rui Wu⁴， Yanru Liu⁵， Ran Liu¹， Qing Peng¹， Jianwen Deng¹，

 Lingchao Meng¹， Zhaoxia Wang¹， Wei Zhang^1*， Yun Yuan^1*

Deep-intronic variants that create or enhance a splice site are increasingly reported as a significant cause of monogenic diseases. However， deep-intronic variants that activate pseudoexons by affecting a branch point are extremely rare in Mendelian diseases. Here， we report on the genetic diagnosis of a patient with dystrophinopathy. Routine genetic testing did not discover a pathogenic DMD variant in him. We then performed muscle-derived dystrophin mRNA analysis and genomic Sanger sequencing of the patient， which revealed a novel deep-intronic splicing variant c.5325+1759G>T in DMD. The novel variant created a new branch point sequence and thus activated a new dystrophin pseudoexon， which confirmed the genetic diagnosis of dystrophinopathy in the patient. Our study highlights the significant role of branch point alterations in aberrant splicing of monogenic genes.