NGS-based targeted sequencing identified six novel variants in patients with Duchenne/Becker muscular dystrophy from southwestern China
Abstract Background At present, Multiplex ligation-dependent probe amplification (MLPA) and exome sequencing are common gene detection methods in patients with Duchenne muscular dystrophy or Becker muscular dystrophy (DMD/BMD), but they can not cover the whole-genome sequence of the DMD gene. In thi...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-023-01556-1 |
| _version_ | 1797811241732800512 |
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| author | Feng Tang Yuanyuan Xiao Cong Zhou Haixia Zhang Jing Wang Yang Zeng |
| author_facet | Feng Tang Yuanyuan Xiao Cong Zhou Haixia Zhang Jing Wang Yang Zeng |
| author_sort | Feng Tang |
| collection | DOAJ |
| description | Abstract Background At present, Multiplex ligation-dependent probe amplification (MLPA) and exome sequencing are common gene detection methods in patients with Duchenne muscular dystrophy or Becker muscular dystrophy (DMD/BMD), but they can not cover the whole-genome sequence of the DMD gene. In this study, the whole genome capture of the DMD gene and next-generation sequencing (NGS) technology were used to detect the patients with DMD/BMD in Southwest China, to clarify the application value of this technology and further study the gene variant spectrum. Methods From 2017 to 2020, 51 unrelated patients with DMD/BMD in southwestern China were clinically diagnosed at West China Second University Hospital of Sichuan University (Chengdu, China). The whole-genome of the DMD gene was captured from the peripheral blood of all patients, and next-generation sequencing was performed. Large copy number variants (CNVs) in the exon regions of the DMD gene were verified through MLPA, and small variations (such as single nucleotide variation and < 50 bp fragment insertions/deletions) were validated using Sanger sequencing. Results Among the 51 patients, 49 (96.1% [49/51]) had pathogenic or likely pathogenic variants in the DMD gene. Among the 49 positive samples, 17 patients (34.7% [17/49]) had CNVs in the exon regions and 32 patients (65.3% [32/49]) had small variations. A total of six novel variants were identified: c.10916_10917del, c.1790T>A, c.1842del, c.5015del, c.5791_5792insCA, and exons 38–50 duplication. Conclusions Pathogenic or likely pathogenic variants of the DMD gene were detected in 49 patients (96.1% [49/51]), of which 6 variants (12.2% [6/49]) had not been previously reported. This study confirmed the value of NGS-based targeted sequencing for the DMD gene expanding the spectrum of variants in DMD, which may provide effective genetic counseling and prenatal diagnosis for families. |
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| id | doaj.art-02673eacbac84ab1bd45086066afbbeb |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-03-13T07:19:43Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
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| series | BMC Medical Genomics |
| spelling | doaj.art-02673eacbac84ab1bd45086066afbbeb2023-06-04T11:41:20ZengBMCBMC Medical Genomics1755-87942023-05-0116111310.1186/s12920-023-01556-1NGS-based targeted sequencing identified six novel variants in patients with Duchenne/Becker muscular dystrophy from southwestern ChinaFeng Tang0Yuanyuan Xiao1Cong Zhou2Haixia Zhang3Jing Wang4Yang Zeng5Department of Medical Genetics, West China Second University Hospital of Sichuan UniversityDepartment of Medical Genetics, West China Second University Hospital of Sichuan UniversityDepartment of Medical Genetics, West China Second University Hospital of Sichuan UniversityDepartment of Medical Genetics, West China Second University Hospital of Sichuan UniversityDepartment of Medical Genetics, West China Second University Hospital of Sichuan UniversityDepartment of Medical Genetics, West China Second University Hospital of Sichuan UniversityAbstract Background At present, Multiplex ligation-dependent probe amplification (MLPA) and exome sequencing are common gene detection methods in patients with Duchenne muscular dystrophy or Becker muscular dystrophy (DMD/BMD), but they can not cover the whole-genome sequence of the DMD gene. In this study, the whole genome capture of the DMD gene and next-generation sequencing (NGS) technology were used to detect the patients with DMD/BMD in Southwest China, to clarify the application value of this technology and further study the gene variant spectrum. Methods From 2017 to 2020, 51 unrelated patients with DMD/BMD in southwestern China were clinically diagnosed at West China Second University Hospital of Sichuan University (Chengdu, China). The whole-genome of the DMD gene was captured from the peripheral blood of all patients, and next-generation sequencing was performed. Large copy number variants (CNVs) in the exon regions of the DMD gene were verified through MLPA, and small variations (such as single nucleotide variation and < 50 bp fragment insertions/deletions) were validated using Sanger sequencing. Results Among the 51 patients, 49 (96.1% [49/51]) had pathogenic or likely pathogenic variants in the DMD gene. Among the 49 positive samples, 17 patients (34.7% [17/49]) had CNVs in the exon regions and 32 patients (65.3% [32/49]) had small variations. A total of six novel variants were identified: c.10916_10917del, c.1790T>A, c.1842del, c.5015del, c.5791_5792insCA, and exons 38–50 duplication. Conclusions Pathogenic or likely pathogenic variants of the DMD gene were detected in 49 patients (96.1% [49/51]), of which 6 variants (12.2% [6/49]) had not been previously reported. This study confirmed the value of NGS-based targeted sequencing for the DMD gene expanding the spectrum of variants in DMD, which may provide effective genetic counseling and prenatal diagnosis for families.https://doi.org/10.1186/s12920-023-01556-1DMDBMDCaptureNGSGenetic counselingPrenatal diagnosis |
| spellingShingle | Feng Tang Yuanyuan Xiao Cong Zhou Haixia Zhang Jing Wang Yang Zeng NGS-based targeted sequencing identified six novel variants in patients with Duchenne/Becker muscular dystrophy from southwestern China BMC Medical Genomics DMD BMD Capture NGS Genetic counseling Prenatal diagnosis |
| title | NGS-based targeted sequencing identified six novel variants in patients with Duchenne/Becker muscular dystrophy from southwestern China |
| title_full | NGS-based targeted sequencing identified six novel variants in patients with Duchenne/Becker muscular dystrophy from southwestern China |
| title_fullStr | NGS-based targeted sequencing identified six novel variants in patients with Duchenne/Becker muscular dystrophy from southwestern China |
| title_full_unstemmed | NGS-based targeted sequencing identified six novel variants in patients with Duchenne/Becker muscular dystrophy from southwestern China |
| title_short | NGS-based targeted sequencing identified six novel variants in patients with Duchenne/Becker muscular dystrophy from southwestern China |
| title_sort | ngs based targeted sequencing identified six novel variants in patients with duchenne becker muscular dystrophy from southwestern china |
| topic | DMD BMD Capture NGS Genetic counseling Prenatal diagnosis |
| url | https://doi.org/10.1186/s12920-023-01556-1 |
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