Variants of the DMD gene in 18 patients, clinical severity prediction, genotype-phenotype correlation, and potential therapies

Abstract

Background: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive rare diseases caused by various mutations in the DMD gene which induce quantity reduction or absence of the dystrophin protein.Aims: To present variants of the DMD gene, predict clinical severity, and discuss genotype-phenotype correlation as well as potential therapies.Material and Methods: Data was collected from patients of Mother Teresa University Hospital Center, Tirana, Albania, whose diagnosis were confirmed through molecular examinations.Results: In this study, 18 male patients were enrolled. Gross mutations were detected in 11 patients, while point mutations were detected in 7 patients. The detected variants were pathogenic in 13 patients and likely pathogenic in 5 patients. The age at clinical onset was approximately 2 years old in 10 patients, 3 years old in 6 patients, 9 years old in 1 patient, and 14 years old in 1 patient. Age at the loss of ambulation was approximately 10 years in 3 patients, 11 years in 3 patients, 12 years in 2 patients, and 14 years old in 1 patient, while 9 patients are still ambulant. Signs and symptoms included muscular, skeletal, nervous, cardiovascular, and respiratory systems. Altogether, 16 patients were diagnosed with DMD and 2 patients were diagnosed with BMD.Conclusion: The genetic analysis cannot predict the course and severity of the dystrophinopathy. Genetic test results must always be evaluated in the context of clinical findings, family history, and other data, yet they are crucial for therapy customization.