Exome sequencing identifies a rare variant in DMD gene causing a severe phenotype of Duchenne Muscular Dystrophy in a Malian family

Introduction: Duchenne Muscular Dystrophy (DMD) is a severe X-linked recessive muscle disease caused by mutations in the DMD gene. Several mutations have been reported since the discovery of the DMD gene in 1986. Although, exonic deletions and duplications are the most common variants associated with DMD, rare cases of point mutations have been reported. In this report, we describe the clinical and molecular features of DMD in a Malian family. Methodology: Informed consent was obtained before enrollment. Patients were thoroughly assessed by specialists including neurologists, cardiologists, and blood CK level was checked. Peripheral blood was collected to extract DNA for genetic testing. Sanger sequencing was performed to confirm the putative variant, and deleteriousness prediction was assessed using in silico tools. Result: A large non-consanguineous Fulani family of 11 individuals were enrolled. Two boys were found to be affected. Symptoms started in their early infancy with predominantly proximal muscle weakness and calf hypertrophy, leading to waddling gait, difficulties running and climbing stairs. These symptoms ultimately resulted in complete loss of mobility and death in late teenage. Blood CK levels were elevated in both patients. The pedigree relationship with the clinical picture was suggestive of DMD. Genetic testing identified a rare pathogenic variant in the DMD gene, subsequently confirmed by sanger sequencing. Conclusion: This report expands the epidemiological spectrum of dystrophinopathies in Africa. It also highlights the need for more access to genetic testing in order to uncover more DMD variants in the African population and prepare our patients for ongoing clinical trials. Keywords: DMD, rare variant, Mali, Africa.