Exploring of deletion mutation causative for Duchenne Muscular Dystrophy (DMD) in Bangladesh cohort

Abstract

Background: Duchenne muscular dystrophy (DMD) is an inherited genetic disorder resulting progressive skeletal, respiratory and cardiac muscle weakness. DMD is caused by a variety of mutations in DMD gene located on the X chromosome, which lead to a lack of functional dystrophin protein expression in males. Approximately 65-70% of individuals with DMD have intragenic deletions in the dystrophin gene. The aim of this study is to identify the frequency of deletion mutations in clinically DMD suspected Bangladeshi cohort. Method: We have conducted multiplex PCR test for the deletion analysis of 35 DMD suspected male patients. A panel comprised of 26 hotspot exons of DMD gene have been used for the analysis. Variant classification analysis was conducted based on the American College of Medical Genetics (ACMG) guidelines. Results: The cohort comprises 35 male patients. Multiplex PCR analysis revealed pathogenic deletion in 60% (21) patients. No clinically relevant variants were found in 40% (14) patients. The diagnostic yield for this test is 60%. The frequency of deletions in exon 48 (38%) was the most common deletion associated with our cohort. Most common symptoms seen among them were positive Gower sign (86%), poor walking and running ability (83%), high CPK level (71%), calf hypertrophy (57%). Conclusions: Deletion mutations are present in 60% of cases. The aim of this study is using the first-tier test for DMD diagnosis to generate the frequency of deletion mutations in Bangladeshi DMD cases. The result shows the utility of using multiplex PCR test as genetic diagnosis that will help clinicians in monitoring and organizing future therapeutic management of DMD suspected cases. To our knowledge, this study is the first report of DMD gene deletion analysis in Bangladesh.