Genetic Profile of the Dystrophin Gene Reveals New Mutations in Colombian Patients Affected with Muscular Dystrophinopathy

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.

Higher Prevalence of Nonsense Pathogenic DMD Variants in a Single-Center Cohort from Brazil: A Genetic Profile Study That May Guide the Choice of Disease-Modifying Treatments

“…The present study detected a prevalence of nonsense variants of 24.5%, which is slightly higher. The percentage of nonsense variants in our population was also significantly higher when compared to other South American countries, where the presence of nonsense singlenucleotide variants varied from 11.6 to 16.7% [5,18,23]. A single-center study conducted in Mexico, however, found similar results regarding the prevalence of nonsense pathogenic variants (n = 11/49; 22.45%) [24].…”

An update on Becker muscular dystrophy

“…BMD has a lower incidence rate than DMD, but due to longer life expectancy, is not much less prevalent. Better access to massive parallel sequencing has increased the diagnosis of BMD in ethnic groups beyond high-income countries [8][9][10][11][12] and has also improved the diagnosis of BMD through prenatal [13] and neonatal screening programs [14,15].…”