Comprehensive genetic characteristics of dystrophinopathies in China
Abstract Background Dystrophinopathies are a set of severe and incurable X-linked neuromuscular disorders caused by mutations in the dystrophin gene (DMD). These mutations form a complex spectrum. A national registration network is essential not only to provide more information about the prevalence...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-07-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13023-018-0853-z |
| _version_ | 1819263587340779520 |
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| author | Peipei Ma Shu Zhang Hao Zhang Siying Fang Yuru Dong Yan Zhang Weiwei Hao Shiwen Wu Yuying Zhao |
| author_facet | Peipei Ma Shu Zhang Hao Zhang Siying Fang Yuru Dong Yan Zhang Weiwei Hao Shiwen Wu Yuying Zhao |
| author_sort | Peipei Ma |
| collection | DOAJ |
| description | Abstract Background Dystrophinopathies are a set of severe and incurable X-linked neuromuscular disorders caused by mutations in the dystrophin gene (DMD). These mutations form a complex spectrum. A national registration network is essential not only to provide more information about the prevalence and natural history of the disease, but also to collect genetic data for analyzing the mutational spectrum. This information is extremely beneficial for basic scientific research, genetic diagnosis, trial planning, clinical care, and gene therapy. Methods We collected data from 1400 patients (1042 patients with confirmed unrelated Duchenne muscular dystrophy [DMD] or Becker muscular dystrophy [BMD]) registered in the Chinese Genetic Disease Registry from March 2012 to August 2017 and analyzed the genetic mutational characteristics of these patients. Results Large deletions were the most frequent type of mutation (72.2%), followed by nonsense mutations (11.9%), exon duplications (8.8%), small deletions (3.0%), splice-site mutations (2.1%), small insertions (1.3%), missense mutations (0.6%), and a combination mutation of a deletion and a duplication (0.1%). Exon 45–50 deletion was the most frequent deletion type, while exon 2 duplication was the most common duplication type. Two deletion hotspots were calculated—one located toward the central part (exon 45–52) of the gene and the other toward the 5’end (exon 8–26). We found no significant difference between hereditary and de novo mutations on deletion hotspots. Nonsense mutations accounted for 62.9% of all small mutations (197 patients). Conclusion We built a comprehensive national dystrophinopathy mutation database in China, which is essential for basic and clinical research in this field. The mutational spectrum and characteristics of this DMD/BMD group were largely consistent with those in previous international DMD/BMD studies, with some differences. Based on our results, about 12% of DMD/BMD patients with nonsense mutations may benefit from stop codon read-through therapy. Additionally, the top three targets for exon-skipping therapy are exon 51 (141, 13.5%), exon 53 (115, 11.0%), and exon 45 (84, 8.0%). |
| first_indexed | 2024-12-23T20:15:58Z |
| format | Article |
| id | doaj.art-dda22994a8a0408a83022283fe88f252 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-23T20:15:58Z |
| publishDate | 2018-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-dda22994a8a0408a83022283fe88f2522022-12-21T17:32:42ZengBMCOrphanet Journal of Rare Diseases1750-11722018-07-0113111010.1186/s13023-018-0853-zComprehensive genetic characteristics of dystrophinopathies in ChinaPeipei Ma0Shu Zhang1Hao Zhang2Siying Fang3Yuru Dong4Yan Zhang5Weiwei Hao6Shiwen Wu7Yuying Zhao8Department of Neurology, the General Hospital of Chinese People’s Armed Police ForceDepartment of Neurology, the General Hospital of Chinese People’s Armed Police ForceDepartment of Neurology, the General Hospital of Chinese People’s Armed Police ForceDepartment of Neurology, the General Hospital of Chinese People’s Armed Police ForceDepartment of Magnetic Resonance, the General Hospital of Chinese People’s Armed Police ForceDepartment of Precision Medicine Laboratory, the General Hospital of Chinese People’s Armed Police ForceDepartment of Precision Medicine Laboratory, the General Hospital of Chinese People’s Armed Police ForceDepartment of Neurology, the General Hospital of Chinese People’s Armed Police ForceResearch Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Shandong UniversityAbstract Background Dystrophinopathies are a set of severe and incurable X-linked neuromuscular disorders caused by mutations in the dystrophin gene (DMD). These mutations form a complex spectrum. A national registration network is essential not only to provide more information about the prevalence and natural history of the disease, but also to collect genetic data for analyzing the mutational spectrum. This information is extremely beneficial for basic scientific research, genetic diagnosis, trial planning, clinical care, and gene therapy. Methods We collected data from 1400 patients (1042 patients with confirmed unrelated Duchenne muscular dystrophy [DMD] or Becker muscular dystrophy [BMD]) registered in the Chinese Genetic Disease Registry from March 2012 to August 2017 and analyzed the genetic mutational characteristics of these patients. Results Large deletions were the most frequent type of mutation (72.2%), followed by nonsense mutations (11.9%), exon duplications (8.8%), small deletions (3.0%), splice-site mutations (2.1%), small insertions (1.3%), missense mutations (0.6%), and a combination mutation of a deletion and a duplication (0.1%). Exon 45–50 deletion was the most frequent deletion type, while exon 2 duplication was the most common duplication type. Two deletion hotspots were calculated—one located toward the central part (exon 45–52) of the gene and the other toward the 5’end (exon 8–26). We found no significant difference between hereditary and de novo mutations on deletion hotspots. Nonsense mutations accounted for 62.9% of all small mutations (197 patients). Conclusion We built a comprehensive national dystrophinopathy mutation database in China, which is essential for basic and clinical research in this field. The mutational spectrum and characteristics of this DMD/BMD group were largely consistent with those in previous international DMD/BMD studies, with some differences. Based on our results, about 12% of DMD/BMD patients with nonsense mutations may benefit from stop codon read-through therapy. Additionally, the top three targets for exon-skipping therapy are exon 51 (141, 13.5%), exon 53 (115, 11.0%), and exon 45 (84, 8.0%).http://link.springer.com/article/10.1186/s13023-018-0853-zDystrophinopathiesDuchenne muscular dystrophyBecker muscular dystrophyMutation spectrum |
| spellingShingle | Peipei Ma Shu Zhang Hao Zhang Siying Fang Yuru Dong Yan Zhang Weiwei Hao Shiwen Wu Yuying Zhao Comprehensive genetic characteristics of dystrophinopathies in China Orphanet Journal of Rare Diseases Dystrophinopathies Duchenne muscular dystrophy Becker muscular dystrophy Mutation spectrum |
| title | Comprehensive genetic characteristics of dystrophinopathies in China |
| title_full | Comprehensive genetic characteristics of dystrophinopathies in China |
| title_fullStr | Comprehensive genetic characteristics of dystrophinopathies in China |
| title_full_unstemmed | Comprehensive genetic characteristics of dystrophinopathies in China |
| title_short | Comprehensive genetic characteristics of dystrophinopathies in China |
| title_sort | comprehensive genetic characteristics of dystrophinopathies in china |
| topic | Dystrophinopathies Duchenne muscular dystrophy Becker muscular dystrophy Mutation spectrum |
| url | http://link.springer.com/article/10.1186/s13023-018-0853-z |
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