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A novel deep intronic single-nucleotide variant introduce dystrophin pseudoexon in Becker muscular dystrophy

作者:Chang Liu 等 日期:2024-04-10 浏览量:106

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 Liu1†, Yanyu Lu1†, Haiyan Yu2, Zhihao Xie3, Chengyue Sun4, Shu Fang5

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

Zhaoxia Wang1, Yun Yuan1*, Zhiying Xie1†

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.