Mutation spectrum analysis of DMD gene in Indonesian Duchenne and Becker muscular dystrophy patients [version 3; peer review: 2 approved]
Background Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic disorders caused by mutations in the DMD gene. The full mutation spectrum of the DMD gene in Indonesian patients is currently unknown. Mutation-specific therapies are currently being developed, such as exon...
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2023-11-01
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| Online Access: | https://f1000research.com/articles/11-148/v3 |
| _version_ | 1827675651748921344 |
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| author | Kristy Iskandar Sunartini Hapsara Chun Ping Liu Rusdy Ghazali Malueka Ery Kus Dwianingsih . Gunadi Masafumi Matsuo Poh San Lai |
| author_facet | Kristy Iskandar Sunartini Hapsara Chun Ping Liu Rusdy Ghazali Malueka Ery Kus Dwianingsih . Gunadi Masafumi Matsuo Poh San Lai |
| author_sort | Kristy Iskandar |
| collection | DOAJ |
| description | Background Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic disorders caused by mutations in the DMD gene. The full mutation spectrum of the DMD gene in Indonesian patients is currently unknown. Mutation-specific therapies are currently being developed, such as exon skipping or stop codon read-through therapy. This study was conducted with the aim of identifying the mutation spectrum of the DMD gene in Indonesia to guide future development and application of feasible therapeutic strategies. Methods This study is a cross sectional study that enrolled 43 male patients with a clinical suspicion of DMD or BMD. Multiplex ligation-dependent probe amplification (MLPA) reaction was performed to screen for the common mutations in the DMD gene. Results Out of 43 subjects, deletions accounted for 69.77% (n=30) cases, while duplications were found in 11.63% (n=5) cases. One novel duplication spanning exons 2 to 62 was identified. Deletion mutations clustered around the distal (66.67%) and proximal (26.67%) hot spot regions of the DMD gene while duplication mutations were observed solely at the proximal region. Two false positive cases of single exon deletion detected through MLPA were attributed to sequence mutations affecting primer ligation sites, confirming the need to validate all single exon deletions when using this screening method. Analysis of available maternal DNA samples showed that the rate of de novo mutations (48.15%) appears higher than expected in this population. Out of 31 patients who were classified as DMD based on clinical and genotype characterizations, 60.47% (n=26) of cases were suitable for exon skipping therapy. Conclusion This is the first comprehensive study showing the feasibility of implementing the MLPA method for routine screening of DMD patients in Indonesia. This is also the first study showing the potential applicability of exon skipping therapy in the majority of DMD cases in the country. |
| first_indexed | 2024-03-10T05:08:55Z |
| format | Article |
| id | doaj.art-5d778e3de77b4449ab4539002cc11676 |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-03-10T05:08:55Z |
| publishDate | 2023-11-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-5d778e3de77b4449ab4539002cc116762023-11-23T01:00:01ZengF1000 Research LtdF1000Research2046-14022023-11-0111158228Mutation spectrum analysis of DMD gene in Indonesian Duchenne and Becker muscular dystrophy patients [version 3; peer review: 2 approved]Kristy Iskandar0Sunartini Hapsara1Chun Ping Liu2Rusdy Ghazali Malueka3Ery Kus Dwianingsih4https://orcid.org/0000-0002-0484-7773. Gunadi5Masafumi Matsuo6Poh San Lai7https://orcid.org/0000-0003-3352-2000Genetics Working Group, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, 55281, IndonesiaAcademic Hospital, Universitas Gadjah Mada, Yogyakarta, 55291, IndonesiaDepartment of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, SingaporeGenetics Working Group, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, 55281, IndonesiaGenetics Working Group, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, 55281, IndonesiaGenetics Working Group, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, 55281, IndonesiaKNC Department of Nucleic Acid Drug Discovery, Faculty of Rehabilitation, Kobegakuin University, Kobe, 651-2180, JapanDepartment of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, SingaporeBackground Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic disorders caused by mutations in the DMD gene. The full mutation spectrum of the DMD gene in Indonesian patients is currently unknown. Mutation-specific therapies are currently being developed, such as exon skipping or stop codon read-through therapy. This study was conducted with the aim of identifying the mutation spectrum of the DMD gene in Indonesia to guide future development and application of feasible therapeutic strategies. Methods This study is a cross sectional study that enrolled 43 male patients with a clinical suspicion of DMD or BMD. Multiplex ligation-dependent probe amplification (MLPA) reaction was performed to screen for the common mutations in the DMD gene. Results Out of 43 subjects, deletions accounted for 69.77% (n=30) cases, while duplications were found in 11.63% (n=5) cases. One novel duplication spanning exons 2 to 62 was identified. Deletion mutations clustered around the distal (66.67%) and proximal (26.67%) hot spot regions of the DMD gene while duplication mutations were observed solely at the proximal region. Two false positive cases of single exon deletion detected through MLPA were attributed to sequence mutations affecting primer ligation sites, confirming the need to validate all single exon deletions when using this screening method. Analysis of available maternal DNA samples showed that the rate of de novo mutations (48.15%) appears higher than expected in this population. Out of 31 patients who were classified as DMD based on clinical and genotype characterizations, 60.47% (n=26) of cases were suitable for exon skipping therapy. Conclusion This is the first comprehensive study showing the feasibility of implementing the MLPA method for routine screening of DMD patients in Indonesia. This is also the first study showing the potential applicability of exon skipping therapy in the majority of DMD cases in the country.https://f1000research.com/articles/11-148/v3Duchenne muscular dystrophy Becker muscular dystrophy DMD gene mutation analysis Indonesia MLPAeng |
| spellingShingle | Kristy Iskandar Sunartini Hapsara Chun Ping Liu Rusdy Ghazali Malueka Ery Kus Dwianingsih . Gunadi Masafumi Matsuo Poh San Lai Mutation spectrum analysis of DMD gene in Indonesian Duchenne and Becker muscular dystrophy patients [version 3; peer review: 2 approved] F1000Research Duchenne muscular dystrophy Becker muscular dystrophy DMD gene mutation analysis Indonesia MLPA eng |
| title | Mutation spectrum analysis of DMD gene in Indonesian Duchenne and Becker muscular dystrophy patients [version 3; peer review: 2 approved] |
| title_full | Mutation spectrum analysis of DMD gene in Indonesian Duchenne and Becker muscular dystrophy patients [version 3; peer review: 2 approved] |
| title_fullStr | Mutation spectrum analysis of DMD gene in Indonesian Duchenne and Becker muscular dystrophy patients [version 3; peer review: 2 approved] |
| title_full_unstemmed | Mutation spectrum analysis of DMD gene in Indonesian Duchenne and Becker muscular dystrophy patients [version 3; peer review: 2 approved] |
| title_short | Mutation spectrum analysis of DMD gene in Indonesian Duchenne and Becker muscular dystrophy patients [version 3; peer review: 2 approved] |
| title_sort | mutation spectrum analysis of dmd gene in indonesian duchenne and becker muscular dystrophy patients version 3 peer review 2 approved |
| topic | Duchenne muscular dystrophy Becker muscular dystrophy DMD gene mutation analysis Indonesia MLPA eng |
| url | https://f1000research.com/articles/11-148/v3 |
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