Abstract
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.
Highlights
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive disorders arising due to mutations in the DMD gene.[1]
Demographic and clinical profile All 43 subjects recruited for this study were male and showed clinical features of DMD/BMD such as difficulty in walking, muscle weakness, positive Gower sign at age of onset and increased creatine kinase (CK) levels in their blood samples
The identified mutations were screened against two well-known DMD databases, namely UMD-DMD France and Leiden Muscular Dystrophy pages database
Summary
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive disorders arising due to mutations in the DMD gene.[1] The DMD gene is one of the largest genes in the human genome with a size of more than 2 Mb. Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive disorders arising due to mutations in the DMD gene.[1] The DMD gene is one of the largest genes in the human genome with a size of more than 2 Mb This gene spans 79 exons and codes for a 14 kb mRNA that translates a cytoplasmic protein called dystrophin. Due to this large size, mutation detection poses a challenge for routine molecular diagnosis in a clinical setting in many developing countries. Two false positive cases of single exon deletion detected through MLPA were attributed to sequence article can be found at the end of the article
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
