Mutations in the dystrophin gene result in Duchenne muscular dystrophy (DMD). Dystrophin is a multidomain protein that functions to stabilize the sarcolemmal membrane during muscle contraction. The central rod domain has been proposed to act as a shock absorber, as a force transducer or as a spacer separating important Nand C-terminal domains that interact with actin and the dystrophin–glycopro...

We have previously shown in a large X-linked pedigree that a deletion removing the dystrophin muscle promoter, the first muscle exon and part of intron 1 caused a severe dilated cardiomyopathy with no associated muscle weakness. Dystrophin expression was present in the muscle of affected males and transcription studies indicated that this dystrophin originated from the brain and Purkinje cell i...

Duchenne muscular dystrophy (DMD) is a lethal, X-linked, muscle-wasting disorder caused by mutations in the large, 2.4-Mb dystrophin gene. The majority of DMD-causing mutations are sporadic, multi-exon, frameshifting deletions, with the potential for variable immunological tolerance to the dystrophin protein from patient to patient. While systemic gene therapy holds promise in the treatment of ...

C ARDIAC muscle is commonly affected in muscular dy~trophies.l-~ X-linked Duchenne's inuscular dystrophy and Becker's muscular dystrophy are caused by mutations in the gene encoding dystrophin,5,6 a membrane cytoskeletal p r ~ t e i n . ~ In skeletal and cardiac muscle, dystrophin is associated with a large oligomeric complex of sarcolemmal g lycopr~te ins .~~~ This dystrophin-glycoprotein comp...

Dystrophin and beta-dystroglycan are components of a complex of at least nine proteins (the dystrophin-glycoprotein complex) that physically link the membrane cytoskeleton in skeletal and cardiac muscle, through the plasma membrane, to the extracellular matrix. Mutations in the dystrophin gene, which result in an absence or a quantitative or qualitative alteration of dystrophin, cause a subset ...

Dystrophin, the protein defective in Duchenne muscular dystrophy (DMD), plays a critical role in the formation and maintenance of the neuromuscular junction. In addition to dystrophin, activation of internal promoters of the DMD gene leads to the production of several short products. Among these, Dp71, which consists of the C-terminal domain of dystrophin, is the most abundant product of the ge...

Dystrophin transcripts were shown to be alternatively spliced in a pattern characteristic of both tissue type and developmental stage. Multiple novel spliced forms of dystrophin mRNA were identified in murine brain tissue, skeletal and cardiac muscle, diaphragm, and human cardiac Purkinje fibers. The transcript diversity was greatest in adult, non-skeletal muscle tissues. Sequence analysis reve...

Duchenne/Becker muscular dystrophies (D/BMD) are X-linked recessive disorders resulting from dystrophin gene mutations. Intragenic recombination in the dystrophin gene occurs with a high frequency. Therefore, determination of the location and frequency of recombination improves D/BMD carrier detection and prenatal diagnosis in families in which the disease-causing mutation cannot be detected by...

Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disease caused by frameshift or nonsense mutations in the DMD gene, resulting loss of dystrophin from muscle membranes. Exon skipping using splice-switching oligonucleotides (SSOs) restores reading frame pre-mRNA generating internally truncated but functional protein. To potentiate effective tissue-specific targeting SSOs, it essentia...

Duchenne Muscular dystrophy (DMD) is an X-linked recessive disorder caused by mutations in the dystrophin gene, which is located in Xp21. The majority of the identified mutations are large deletions and duplications, and gene dosage assays were developed for quantitative genomic screening of copy number variations. However, remaining 25% of the DMD are due to point mutations and require direct ...