Uncovering the true features of dystrophin gene rearrangement and improving the molecular diagnosis of Duchenne and Becker muscular dystrophies
Chao Ling,
Yi Dai,
Chang Geng,
Shirang Pan,
Weipeng Quan,
Qingyun Ding,
Xunzhe Yang,
Dongchao Shen,
Qing Tao,
Jingjing Li,
Jia Li,
Yinbing Wang,
Shan Jiang,
Yang Wang,
Lin Chen,
Liying Cui,
Depeng Wang
Affiliations
Chao Ling
The Laboratory of Clinical Genetics, Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China
Yi Dai
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China; Corresponding author
Chang Geng
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China
Shirang Pan
Grandomics Biosciences, Beijing 102200, China
Weipeng Quan
Grandomics Biosciences, Beijing 102200, China
Qingyun Ding
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China
Xunzhe Yang
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China
Dongchao Shen
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China
Qing Tao
Grandomics Biosciences, Beijing 102200, China
Jingjing Li
Grandomics Biosciences, Beijing 102200, China
Jia Li
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China
Yinbing Wang
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China
Shan Jiang
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China
Yang Wang
Grandomics Biosciences, Beijing 102200, China
Lin Chen
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China
Liying Cui
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China
Summary: Duchenne and Becker muscular dystrophies (DMD/BMD) are caused by complex mutations in the dystrophin gene (DMD). Currently, there is no integrative method for the precise detection of all potential DMD variants, a gap which we aimed to address using long-read sequencing. The captured long-read sequencing panel developed in this study was applied to 129 subjects, including 11 who had previously unsolved cases. The results showed that this method accurately detected DMD mutations, ranging from single-nucleotide variations to structural variations. Furthermore, our findings revealed that continuous exon duplication/deletion in the DMD/BMD cohort may be attributed to complex segmental rearrangements and that noncontiguous duplication/deletion is generally attributed to intragenic inversion or interchromosome translocation. Mutations in the deep introns were confirmed to produce a pseudoexon. Moreover, variations in female carriers were precisely identified. The integrated and precise DMD gene screening method proposed in this study could improve the molecular diagnosis of DMD/BMD.
