Deletion Mutations in DMD Gene and Disease Phenotype Among Saudi Patients with Duchenne Muscular Dystrophy

The importance of deletion mutations in the Duchenne muscular dystrophy (DMD) gene causing DMD have been reported worldwide. This study specifically looks at the distribution spectrum of these mutations in the proximal and distal 'hot spot' regions of the DMD gene in view of disease phenotype among Saudi patients. It further addresses the limitations of multiplex PCR as a widely used screening method to detect these mutations. Fifteen Saudi children aged 2-19 yrs with either clinically confirmed or suspected DMD/BMD, were analyzed for deletions in 26 exons of dystrophin gene using four different sets of multiplex PCR. The study also included normal controls for validation. Disease progression in these patients was clinically monitored since 2007. Twelve out of 15 patients showed deletions in the DMD gene. The remaining three had no deletions in the gene fragments analyzed. Set 1 detected no deletions in any of the patients, whereas each of sets 2, 3 and 4 detected two, four and three deletions respectively. All of these mutations were located in the distal ‘hot spot’ region and none were detected in the proximal ‘hot spot’ region. The normal control samples showed no deletions in any of the 26 exons tested. Therefore distribution and frequency of the most common deletions in a group of Saudi DMD/BMD patients using a multiplex PCR method was demonstrated. The overall distribution of deletion mutations in the distal ‘hot spot’ region was in accordance with cases investigated elsewhere. However, the study suggested that disease progression was directly related to higher incidence of deletions in distal 'hot spot' of the DMD gene which was indicative of severe form of DMD. Failure to detect any mutation in three out of fifteen samples reflected the limitation of the multiplex PCR technique since clinically these patients were DMD/BMD positive. In conclusion, this study emphasizes the need for further investigation into the genotype/phenotype aspects of the Saudi DMD/BMD population through implying alternative methodologies in order to provide better diagnostic, prognostic and prenatal services to the suffering patients and their families.