Congenital muscular dystrophies are autosomal recessive diseases characterized by generalized hypotonia, delayed motor milestones and involvement of the brain. A large subgroup of this rather heterogeneous disease is due to mutations in one of the chains of the extracellular matrix molecules...

Caveolin-3 is the principal structural protein component of caveolae membrane domains in skeletal muscle cells. Caveolae are plasma membrane invaginations implicated in the regulation of signal transduction events. The roles that caveolin-3 plays in skeletal muscle cell physiology are becoming...

Lamins are nuclear intermediate filaments, which form a network like structure underneath the nuclear membrane, the nuclear lamina, as well as complexes in the nuclear interior. Lamins associate with numerous proteins in the inner nuclear membrane, including emerin, and lamina-associated...

Duchenne muscular dystrophy (DMD) is the most prevalent and severe form of human muscular dystrophy. While clinical descriptions of DMD date back to the 1850’s, over 100 years passed before evidence suggested that the muscle cell plasma membrane, or sarcolemma, is compromised in DMD muscle....

Spinal muscular atrophies (SMA) are characterized by degeneration of lower motor neurons and occasionally bulbar motor neurons leading to progressive limb and trunk paralysis associated with muscular atrophy. SMA is a recessive autosomal disorder with an incidence of 1 out of 5000 newborns and...

Many of the muscular dystrophies are caused by defects in proteins involved in main taining connections between the cytoskeleton and extracellular matrix – cell adhe sion complexes. Cell adhesion complexes in many other systems are associated with major signalling pathways involved in...

It is now well established that mutations in the gene encoding the large sarcolemmal-associated protein dystrophin cause Duchenne and Becker muscular dystrophies (DMD and BMD). The core dystrophin glycoprotein complex (DGC) as described by the Campbell and Ozawa groups,1,2 is assembled around...

The sarcoglycans are transmembrane proteins found as a plasma membrane-associated complex. First characterized as a subunit of the dystrophin glycoprotein complex in skeletal muscle, the sarcoglycan complex is secondary disrupted and destabilized from the plasma membrane when dystrophin is...

The dystrophin-associated protein complex (DAPC) plays a critical role in maintaining the structural integrity of the sarcolemma of skeletal muscle. In addition, several regulatory molecules, including neuronal nitric oxide synthase, are localized to the DAPC through the syntrophin family of...

Myotonic dystrophy type 1 (DM1) is the most common inherited muscular dystrophy affecting adults. The underlying mutation is the same in all patients with DM1, namely a trinucleotide (CTG) repeat expansion. There is now conclusive evidence that there are several distinct molecular mechanisms...

Gene therapy for the muscular dystrophies aims to restore the normal biochemistry by either modifying the damaged gene (or mRNA) or by expression of a therapeutic transgene. Animal models, mostly mice, are available for many of the muscular dystrophies and so can be used to test gene therapy...

The limb-girdle muscular dystrophies (LGMD) comprise a group of disorders now known to reflect the whole spectrum of molecular pathogenesis of muscle disease. Initially identified as a heterogeneous set of muscular dystrophies predominantly affecting the pelvic and shoulder girdle musculature,...

Although the primary deficiency in dystrophin and the concomitant reduction in surface glycoproteins are well established factors in the molecular pathogenesis of Duchenne muscular dystrophy, the pathophysiological events that render a muscle fibre more susceptible to necrosis are not well...

The congenital muscular dystrophies (CMD) are a heterogeneous group of autosomal recessive disorders a number of which have recently been shown to be associated with mutations in the genes encoding for either known or putative glycosyltransferases. These include Fukuyama CMD, Muscle-Eye-Brain...

Duchenne muscular dystrophy (DMD) and the allelic Becker muscular dystrophy (BMD) are X-linked recessive disorders caused by mutations in the dystrophin gene. The dystrophin gene spans 2.4 MB on the human X-chromosome and contains 7 promoters, each with a unique first exon, and 78 additional...

Limb girdle muscular dystrophies are caused by mutations in several genes that encode for proteins with divergent functions. The most common LGMD forms result from sarcolemmal adhesion complex defects (sarcoglycans, chapter 10), but also other sarcolemmal molecules (caveolin-3 and dysferlin;...

Duchenne muscular dystrophy (DMD) is a devastating muscle wasting disease caused by the lack of the cytoskeletal protein dystrophin in muscle. The dystrophin-related protein, utrophin, shows a high degree of sequence similarity to dystrophin and it has been postulated that utrophin replacement...