Background:
Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder caused by mutations in the DMD gene, leading to a loss of functional dystrophin protein. Understanding the genetic landscape of DMD is essential for tailoring therapies and predicting clinical outcomes. This meta-analysis investigates the spectrum of genetic variants in DMD and their clinical implications.
Objectives:
To analyze the prevalence and distribution of DMD genetic variants and evaluate their correlations with disease severity, progression, and treatment response.
Methods:
A systematic search of PubMed, Embase, and Cochrane Library identified studies reporting DMD genetic variants and associated clinical outcomes. Eligible studies included data on deletion, duplication, and point mutations across the DMD gene. Meta-analytical techniques were used to synthesize findings, focusing on genotype-phenotype correlations.
Results:
Analysis of 28 studies encompassing over 4,000 patients revealed that deletions accounted for 65% of cases, with hotspots in exons 45–55. Duplications and point mutations represented 25% and 10%, respectively. Genotype-phenotype correlations indicated more severe motor deficits with mutations disrupting the dystrophin rod domain, while exon-skipping amenable mutations were associated with milder disease. Emerging therapies targeting specific mutation types showed promise for personalized treatment.
Conclusion:
This meta-analysis highlights the genetic complexity of DMD and its clinical relevance, underscoring the importance of genetic characterization in advancing personalized therapeutic strategies.