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(087)

1Department of Neurology， Peking University First Hospital，

2Department of Neurology， Peking University People＇s Hospital

3Department of Neurology， Shanghai Sixth People＇s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

4Department of Neurology， China-Japan Friendship Hospital

5GrandOmics Biosciences

 Zhiying Xie^1†， Yunlong Lu^1†， Chang Liu¹， Chengyue Sun²， Jiaxi Yu¹，

Chen Ling¹， Xinghua Luan³， Wei Wang⁴， Li Wang⁵， Yanhong Liang⁵，

Qianbo Luo⁵， Lingchao Meng¹， Zhaoxia Wang^1*， Yun Yuan^1*

A long-standing challenge in the genetic diagnosis of Becker muscular dystrophy (BMD) has been to identify causal variants in deep intronic regions of DMD. A 3.8-year-old boy with a suspected diagnosis of BMD was enrolled in this study. Routine genomic detection approaches failed to reveal disease-causing variants in him. To identify possible deep intronic DMD variants that might be missed by the routine approaches， we performed muscle-derived DMD mRNA analysis and detected an aberrant cryptic exon-containing transcript. Further genomic Sanger sequencing and in silico splicing predictions detected a novel deep-intronic cryptic exon-activating variant c.8217+23338A>G in DMD. Detection and appropriate interpretation of deep intronic DMD variants has potential implications for gene therapies targeting full-length dystrophin expression.