Patterns of Dystrophin Gene Deletion/Duplication in a Sample of Saudi Patients with Duchenne Muscular Dystrophy

Ayman Abdelhady,Salem Abdelhady,Hebatallah Rashed

doi:10.35248/2157-7439.19.8.252

Abstract

Introduction: Duchenne muscular dystrophy (DMD) is caused by the lack of functional dystrophin molecules, either due to nonsense mutations (premature stop codons) or by large rearrangements (deletions or duplications) that disturb the reading frame and in consequence abolish the production of dystrophin in muscles. Methods: Twenty patients with muscular dystrophy diagnosed by clinical history, family pedigree, CK total and histopathology of muscle biopsy is subjected to screening for all 79 exons of dystrophin gene for deletions and duplications. Results and Discussion: Deletion was detected in 80% of patients, while 15% showed duplication, one patient shows nucleotide substitution (c.10033C>T) in exon 69. Most common deletion found between exon 44 and 52. Conclusion: Our study detected high incidence of gene deletion compared to other studies, the most common deletion is multi exon deletion in the major hot spot of the gene (exon 44-52), also we detected lower incidence of duplication with higher percentage of duplication found distally.

Highlights

Duchenne muscular dystrophy (DMD) is caused by the lack of functional dystrophin molecules, either due to nonsense mutations or by large rearrangements that disturb the reading frame and in consequence abolish the production of dystrophin in muscles
Our study detected high incidence of gene deletion compared to other studies, the most common deletion is multi exon deletion in the major hot spot of the gene, we detected lower incidence of duplication with higher percentage of duplication found distally
Dystrophin gene deletion was detected in 16 patients out of 20 (80%), while three patients only (15%) showed duplication

Summary

Introduction

Duchenne muscular dystrophy (DMD) is caused by the lack of functional dystrophin molecules, either due to nonsense mutations (premature stop codons) or by large rearrangements (deletions or duplications) that disturb the reading frame and in consequence abolish the production of dystrophin in muscles. Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder that affects 1 in 3,500 males and is caused mutations in the dystrophin gene. DMD occurs either due to nonsense mutations (premature stop codons) or by large rearrangements (deletions or duplications) that disturb the reading frame of the dystrophin gene and in consequence abolish the production of dystrophin in muscles [1]. Dystrophin has a major structural role in muscle as it links the internal cytoskeleton to the extracellular matrix, strengthening the muscle fibers and protecting them from injury as muscles contract. Dystrophin is thought to serve as a shock absorber protein to protect muscle cells from movement-induced damage [2]

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