Abstract
Background
Duchenne and Becker muscular dystrophies (DMD/BMD) are the most common human dystrophinopathies with recessive X-linked inheritance. Dystrophin gene deletions and duplications are the most common mutations, followed by point mutations. The aim of this study is to characterize the mutational profile of the dystrophin gene in Colombian patients with DMD/BMD.
Material and Methods
Mutational profiling was determined in 69 affected patients using Sanger sequencing, next-generation sequencing (NGS) and/or multiplex ligation dependent-probes amplification (MLPA). Genetic variants were classified according to molecular consequence and new variants were determined through database and literature analysis.
Results
Mutational profile in affected patients revealed that large deletions/duplications analyzed by MLPA accounted for 72.5% of all genetic variations. By using Sanger sequencing or NGS, we identified point mutations in 15.9% and small deletions in 11.6% of the patients. New mutations were found, most of them were point mutations or small deletions (10.1%).
Conclusion
Our results described the genetic profile of the dystrophin gene in Colombian patients with DMD and contribute to efforts to identify molecular variants in Latin American populations. For our population, 18.8% of cases could be treated with FDA or MDA approved molecular therapies based on specific mutations. These data contribute to the establishment of appropriate genetic counseling and potential treatment.
Abbreviations
DMD/BMD, Duchenne and Becker muscular dystrophies; NGS, next-generation sequencing; MLPA, multiplex ligation dependent-probes amplification; NHEJ, the non-homologous end joining mechanism; NAHR, the non-allelic homologous recombination; ORF, open reading frame; ASD, α-syntrophin; DBD, dystrobrevin; PTC, premature termination codons; NMD, Nonsense Mediated Decay system; AIMs Ancestry informative markers.
Ethics Approval and Consent to Participate
All experimental procedures were approved by the Ethics Committee of the Universidad del Rosario. The study followed the guidelines of the Declaration of Helsinki (Approved CEI-AMH002-000185). All participants provided informed consent to take part in this study and for clinical attention in the private laboratory Genética Molecular de Colombia.
Acknowledgments
We thank Genética Molecular de Colombia and Universidad del Rosario for providing all the data and infrastructure necessary for carrying out this study.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors report no conflicts of interest in this work.