Analysis of the mutational spectrum of Duchenne muscular dystrophy in a group of Colombian patients

Introduction: Muscular dystrophy of Duchenne (OMIM: 310200, ORPHA: 98896) is a recessive X-linked primary myopathy. It is the most frequent neuromuscular disorder of genetic etiology, with an incidence of one per 3,500 men and an overall prevalence of 4.78 per 100.000 people. Methods: A clinical evaluation of 63 patients with Duchenne muscular dystrophy was carried out in a Colombian reference center. We performed all the subjects, molecular analysis through MLPA and massive sequencing in parallel. Results: In 47 of the 62 subjects (75%), deletion/duplication variants of exons were detected in the dystrophin gene, using MLPA. We found 33 probands with deletions (53.2%) and 14 cases of duplications (22.5%) of one or more exons. The sequencing study of the DMD gene by the mass sequencing technique in parallel was performed in 15 individuals (24.2%) with negative MLPA. There were nonsense mutations in 6 cases (9.6%), mutations affecting the reading frame in 7 cases (11%) and mutations affecting splicing in 2 cases (3.2%). No missense mutations were found. The variants were distributed throughout the gene, and five variants were found that had not been previously reported, identified in 7 individuals. Conclusions: The molecular diagnosis of point mutations through massively parallel sequencing allowed to reach the diagnostic confirmation efficiently, defining for the negative cases for deletion/duplication, the adequate advice and the implementation of appropriate therapeutic management.