Clinico-Pathologic, Biochemical and Genetic Characterization of Duchenne Muscular Dystrophy in Leban

Dr. Riyad El-Khoury

Start: Sep 01, 2019

End: Sep 01, 2022

Abstract

Duchenne Muscular Dystrophy (DMD) is the most prevalent inherited muscle disease of childhood, affecting approximately 1 in 3500 – 6000 male live births. DMD is caused by mutations in the dystrophin gene, which encodes a large sub-sarcolemmal protein that is thought to play a major functional role in force transduction and a structural role by ensuring the stability of the sarcolemma. Around three quarters of DMD-associated mutations are large deletions/duplications whereas the remaining represent point mutations and small rearrangements. Although the vast majority of muscle fibers from DMD patients do not express dystophin, a small percentage of dystrophin positive fibers, termed ‘revertant’ fibers, are frequently observed. The mechanism by which these fibers reinstate dystrophin expression is still poorly defined. Moreover, while the genetic origin of DMD is clearly established, the precise mechanisms that lead to muscle breakdown are not fully elucidated. Given the range of potential genetic alterations, and amount and size of residual dystrophin, it is not surprising that associated clinical phenotypes extend over a similarly broad range.
Currently, guidelines for healthcare can ameliorate the quality of life but cannot setback the clinical course of the disease. Various encouraging therapeutic strategies are however being developed. Exon skipping is an approach of particular interest, where an FDA approved drug, targeting specifically exon 51, was shown to slow the disease progression in patients. A substantial number of Duchenne patients (83%) could supposedly benefit from this newly developed therapy as the bulk of observed deletions cluster to specific hotspots.
To our knowledge, there are currently no studies whatsoever performed in Lebanon assessing rigorously the disease course and the mutational pattern of Duchenne muscular dystrophy. We have therefore set a research project in order to characterize and correlate the Clinico-pathologic, Biochemical and

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