Uncovering the true features of dystrophin gene rearrangement and improving the molecular diagnosis of Duchenne and Becker muscular dystrophies
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-r...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-12-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223024422 |
| _version_ | 1797388766960156672 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Chao Ling |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T22:45:34Z |
| format | Article |
| id | doaj.art-c381457b3f64488ba8097ca3335ff286 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-08T22:45:34Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-c381457b3f64488ba8097ca3335ff2862023-12-17T06:40:30ZengElsevieriScience2589-00422023-12-012612108365Uncovering the true features of dystrophin gene rearrangement and improving the molecular diagnosis of Duchenne and Becker muscular dystrophiesChao Ling0Yi Dai1Chang Geng2Shirang Pan3Weipeng Quan4Qingyun Ding5Xunzhe Yang6Dongchao Shen7Qing Tao8Jingjing Li9Jia Li10Yinbing Wang11Shan Jiang12Yang Wang13Lin Chen14Liying Cui15Depeng Wang16The 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, ChinaDepartment of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China; Corresponding authorDepartment of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, ChinaGrandomics Biosciences, Beijing 102200, ChinaGrandomics Biosciences, Beijing 102200, ChinaDepartment of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, ChinaDepartment of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, ChinaDepartment of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, ChinaGrandomics Biosciences, Beijing 102200, ChinaGrandomics Biosciences, Beijing 102200, ChinaDepartment of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, ChinaDepartment of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, ChinaDepartment of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, ChinaGrandomics Biosciences, Beijing 102200, ChinaDepartment of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, ChinaDepartment of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, ChinaGrandomics Biosciences, Beijing 102200, ChinaSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004223024422Health sciencesClinical geneticsPediatrics |
| spellingShingle | 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 Uncovering the true features of dystrophin gene rearrangement and improving the molecular diagnosis of Duchenne and Becker muscular dystrophies iScience Health sciences Clinical genetics Pediatrics |
| title | Uncovering the true features of dystrophin gene rearrangement and improving the molecular diagnosis of Duchenne and Becker muscular dystrophies |
| title_full | Uncovering the true features of dystrophin gene rearrangement and improving the molecular diagnosis of Duchenne and Becker muscular dystrophies |
| title_fullStr | Uncovering the true features of dystrophin gene rearrangement and improving the molecular diagnosis of Duchenne and Becker muscular dystrophies |
| title_full_unstemmed | Uncovering the true features of dystrophin gene rearrangement and improving the molecular diagnosis of Duchenne and Becker muscular dystrophies |
| title_short | Uncovering the true features of dystrophin gene rearrangement and improving the molecular diagnosis of Duchenne and Becker muscular dystrophies |
| title_sort | uncovering the true features of dystrophin gene rearrangement and improving the molecular diagnosis of duchenne and becker muscular dystrophies |
| topic | Health sciences Clinical genetics Pediatrics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223024422 |
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