மூலக்கூறு மற்றும் மரபணு மருத்துவம்

Molecular Characteristics of Duchenne Muscular Dystrophy in a Lebanese Cohort

Abstract

El-Khoury R, Ahdab-Barmada M, Souaid M and Farra C

Background: Duchenne Muscular Dystrophy (DMD) is a progressive neuromuscular disorder characterized by a relentless clinical course with diagnosis usually established around three to four years of age. DMD is caused by mutations in the dystrophin gene, where deletions and duplications of one or more exons represent the bulk of related genetic aberrations.
Aims and Methods: Our aim in the current study is to analyze the frequency and the distribution pattern of deletions/duplications associated with dystrophin gene exons and assess the mean diagnostic age of DMD in a small Lebanese group of dystrophic patients suspected with DMD/BMD based on observed clinical features.
Results and Discussion: Among 52 samples analyzed, we identified 33 cases (63%) with deletions and two cases (4%) with duplications. Deletions were of variable sizes, ranging from 1 to 47 exons and occurred mostly (78%) in two deletion hotspots (HS), HS1 (18%) and HS2 (60%), covering exons 6-19 and 45-52 respectively. Single exon deletions were even further restricted (90%) to the deletion hotspots, mainly to HS2 (80%). The average age of DMD molecular diagnosis in our subject study was 7 years of age.
Conclusion: Molecular analyses were consistent with those obtained in previous studies, with however an average age of DMD diagnosis significantly later than what is usually reported. Our study illustrates the need to implement early molecular diagnosis in order to institute optimal care, including available targeted treatments, for our patients.