Deficiency of the 50K dystrophin-associated glycoprotein in severe childhood autosomal recessive muscular dystrophy

  title={Deficiency of the 50K dystrophin-associated glycoprotein in severe childhood autosomal recessive muscular dystrophy},
  author={Kiichiro Matsumura and Fernando M. S. Tom{\'e} and Huguette Collin and Kemal Azibi and Malika Chaouch and Jean Claude Kaplan and Michel Gustave Jules Fardeau and Kevin P. Campbell},
X-LINKED recessive Duchenne muscular dystrophy (DMD) is caused by the absence of dystrophin, a membrane cytoskeletal protein1,2. Dystrophin is associated with a large oligomeric com-plex of sarcolemmal glycoproteins3–10. The dystrophin–glycoprotein complex has been proposed to span the sarcolemma to provide a link fyetween the subsarcolemmal cytoskeleton and the extracellular matrix component, laminin7,9. In DMD, the absence of dystrophin leads to a large reduction in all of the dystrophin… 

Deficiency of dystrophin-associated proteins in Duchenne muscular dystrophy patients lacking COOH-terminal domains of dystrophin.

The results indicate that the COOH-terminal domains of dystrophin are required for the proper interaction of dy strophin with the dystrophic proteins and support the hypothesis that the loss of the dyStrophin-associated proteins in the sarcolemma leads to severe muscular dystrophy even when truncated dystophin is present in the subsarcolemmal cytoskeleton.

The Childhood Muscular Dystrophies: Diseases Sharing a Common Pathogenesis of Membrane Instability

Animal models have been identified also demonstrating defects in specific proteins linking the subsarcolemmal cytoskeleton to the extracellular matrix which will help researchers to understand their human counterparts and provide a system for testing therapeutic strategies.

Mild deficiency of dystrophin-associated proteins in Becker muscular dystrophy patients having in-frame deletions in the rod domain of dystrophin.

The results indicate that (1) the abnormality of the sarcolemmal glycoprotein complex, which is similar to but milder than that in DMD patients, also exists in these BMD patients and (2) the rod domain of dystrophin is not crucial for the interaction with the dyStrophin-associated proteins.

Molecular diagnosis of muscular dystrophies

While there are no reports on the role of mutations of dystroglycan and the syntrophin gene as being a cause of muscular dystrophies, the immunostaining intensities of these complexes are reduced as a secondary phenomenon of defects of Dystrophin in DMD.

Brief report: deficiency of a dystrophin-associated glycoprotein (adhalin) in a patient with muscular dystrophy and cardiomyopathy.

In skeletal and cardiac muscle, dystrophin is associated with a large oligomeric complex of sarcolemmal glycoproteins, a major component of the extracellular matrix.

Immunohistochemical analysis of dystrophin-associated proteins in Becker/Duchenne muscular dystrophy with huge in-frame deletions in the NH2-terminal and rod domains of dystrophin.

The results suggest that the NH2-terminal and rod domains of dystrophin may not be essential for the interaction with the sarcolemmal glycoprotein complex; and defects in the actin binding activity of dy STP may cause disruption of the anchorage of the dyStrophin-glycop protein complex to the subsarcoleMMal cytoskeleton, which may render muscle fibers susceptible to degeneration.



Association of dystrophin and an integral membrane glycoprotein

The results indicate that the function of dystrophin could be to link this glycop protein to the underlying cytoskeleton and thus help either to preserve membrane stability or to keep the glycoprotein non-uniformly distributed in the sarcolemma.

Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle

It is shown that four glycoproteins are integral components of the dystrophin complex and that the concentration of one of these is greatly reduced in DMD patients, suggesting the reduction in this glycoprotein may be one of the first stages of the molecular pathogenesis of muscular dystrophy.

Presence of normal dystrophin in Tunisian severe childhood autosomal recessive muscular dystrophy

The expression of dystrophin in muscle biopsies from patients in Tunisia with severe childhood autosomal recessive muscular dystrophy (SCARMD) is reported, to confirm that SCARMD is distinct from DMD and BMD.

An autosomal transcript in skeletal muscle with homology to dystrophin

THE Duchenne muscular dystrophy (DMD) gene has been localized to chromosome Xp211–6 and codes for a 14-kilobase (kb) transcript7 and a protein called dystrophin8, of relative molecular mass 427,000.

Dystrophin-associated proteins are greatly reduced in skeletal muscle from mdx mice

Investigation of the relative abundance of each of the components of the dystrophin-glycoprotein complex in skeletal muscle from normal and mdx mice suggests that the loss of dystophin-associated proteins is due to the absence of dyStrophin and not due to secondary effects of muscle fiber degradation.

Primary structure of dystrophin-associated glycoproteins linking dystrophin to the extracellular matrix

The hypothesis that the dramatic reduction in the 156K DAG in Duchenne muscular dystrophy leads to a loss of a linkage between the sarcolemma and extra-cellular matrix and that this may render muscle fibres more susceptible to necrosis is supported.