作者：Zhiying Xied等 日期：2023-11-01 浏览量：68
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
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.