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

Abstract

Paula Triana-Fonseca,1 Juan Fernando Parada-Márquez,1 Claudia T Silva-Aldana,2 Daniela Zambrano-Arenas,1 Laura Lucia Arias-Gomez,2 Natalia Morales-Fonseca,3 Esteban Medina-Méndez,2 Carlos M Restrepo,4 Daniel Felipe Silgado-Guzmán,2 Dora Janeth Fonseca-Mendoza4 1Facultad de Medicina, Universidad del Bosque, Bogotá, DC, Colombia; 2Department of Molecular Diagnosis, Genética Molecular de Colombia SAS, Bogotá, DC, Colombia; 3Department of Medicine, Instituto Colombiano de Neurociencias, Bogotá, DC, Colombia; 4Center for Research in Genetics and Genomics – CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, DC, ColombiaCorrespondence: Dora Janeth Fonseca-Mendoza; Daniel Felipe Silgado Guzmán Email [email protected]; [email protected]: 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.Keywords: Duchenne–Becker muscular dystrophy, DMD, MLPA, next-generation sequencing, target molecular therapy, exon skipping, mutation

Keywords

• duchenne-becker muscular dystrophy
• dmd
• mlpa
• next-generation sequencing
• target molecular therapy
• exon skipping
• mutation