RNA-based therapeutic approaches using splice-switching oligonucleotides have been successfully applied to rescue dystrophin in Duchenne muscular dystrophy (DMD) preclinical models and are currently being evaluated in DMD patients. Although the modular structure of dystrophin protein tolerates internal deletions, many mutations that affect nondispensable domains of the protein require further s...

Due to frame-shifting mutations in the DMD gene that cause dystrophin deficiency, Duchenne muscular dystrophy (DMD) patients suffer from lethal muscle degeneration. In contrast, mutations in the allelic Becker muscular dystrophy (BMD) do not disrupt the translational reading frame, resulting in a less severe phenotype. In this study, we explored a genetic therapy aimed at restoring the reading ...

DNA extraction and Southern blot analysis of two cases of McLeod's syndrome showed restriction fragments identical to normal controls using probes from the Xp21 (1-2) region, in contrast to striking deletions found in two other McLeod phenotypes studied in the USA. The McLeod locus is adjacent to Duchenne muscular dystrophy (DMD) and dystrophin immunocytochemistry showed that expression is norm...

Duchenne muscular dystrophy (BMD) is an inherited X-link disease. The incidence of this muscle-wasting disease is 1:5000 male live births. Mutation in the gene coding for dystrophin is the main cause of BMD. Most cases of this disease succumb to respiratory and cardiac failure in 3rd to 4th decades. The slow progression of BMD and recent achievement of gene therapies make it as an appropriate c...

Duchenne muscular dystrophy is a severe muscle-wasting disease caused by mutations in the dystrophin gene that ablate functional protein expression. Although exonic deletions are the most common Duchenne muscular dystrophy lesion, duplications account for 10-15% of reported disease-causing mutations, and exon 2 is the most commonly duplicated exon. Here, we describe the in vitro evaluation of p...

Duchenne and Becker muscular dystrophy severity depends upon the nature and location of the DMD gene lesion and generally correlates with the dystrophin open reading frame. However, there are striking exceptions where an in-frame genomic deletion leads to severe pathology or protein-truncating mutations (nonsense or frame-shifting indels) manifest as mild disease. Exceptions to the dystrophin r...

depending on the sensitivity of the method, deletions may be detected at the majority (60-65 %) of duchenne/becker muscular dystrophy (dmd/bmd) cases. duplications may be seen in approximately 5 -10% and the remaining mutations are point mutations, intronic deletions, exonic insersions of repetetive sequences and combinations of all. severity of the disease does not correlate with the size of t...

Substitutions, deletions and duplications in the dystrophin gene lead to either the severe Duchenne muscular dystrophy (DMD) or mild Becker muscular dystrophy depending on whether out-of-frame or in-frame transcripts are produced. We identified a DMD case (GSΔ44) where the correlation between genotype and phenotype is not respected, even if carrying a typical Duchenne mutation (exon 44 deletion...

• duchenne muscular dystrophy o onset 3 to 5 yrs o clinical § weakness o distribution § proximal > distal § symmetric § legs & arms § most involved muscles: adductor magnus in legs § relatively spared muscles: gracilis & sartorius o course § reduced motor function by 2 to 3 years § steady decline in strength: after 6 to 11 years o gowers sign: standing up with the aid of hands pushing on knees ...