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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A group of 44 monoclonal antibodies (mAbs) raised against the central helical rod (25 mAbs) and C-terminal (19 mAbs) regions of dystrophin were prepared using trpE recombinant fusion proteins as immunogens. Some mAbs cross-react with the structurally related proteins, alpha-actinin and utrophin. Epitope mapping revealed uneven distribution of mAb-binding sites, no mAbs being produced against the C-terminal end of the helical fragment or the cysteine-rich region of the C-terminal dystrophin fragment. The failure of these large regions of the recombinant immunogens to elicit anti-dystrophin antibodies may be because of their inability to fold into the correct dystrophin-like conformation. The mAbs were selected for their ability to recognize 427 kDa dystrophin on Western blots after SDS/PAGE, and/or for immunostaining of the membrane in frozen muscle sections. Although some mAbs obtained by Western-blot screening failed to bind native dystrophin in frozen muscle sections, successful binding could be obtained after SDS or urea treatment of the tissue section to expose the epitopes. This increases the range of mAbs available for detection of dystrophin deletions in muscular dystrophy and evaluation of myoblast therapy.
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PMID:Monoclonal antibodies for dystrophin analysis. Epitope mapping and improved binding to SDS-treated muscle sections. 128 10

Duchenne and the less severe Becker form of muscular dystrophy (DMD,BMD) result from genetic deficiency in the level and/or activity of the protein dystrophin. The recent availability of cDNA based minigenes encoding recombinant dystrophin polypeptides has raised the possibility of somatic gene transfer as a therapeutic approach to treat dystrophin deficiency. In this respect, the mdx mouse provides a useful model of DMD exhibiting features characteristic of both the early myopathic and later fibrotic phases of the human disease. Using a mutated human cDNA, compatible in size with virus-based somatic gene transfer vectors, the pathophysiological consequences of restoring dystrophin expression have been examined in transgenic mdx mice. Transgene expression was correlated with a marked reduction of the skeletal myofibre necrosis and regeneration which is a major feature of the dystrophin-deficient phenotype in young mdx mice. The cDNA construct which is based on a very mild BMD phenotype thus encodes a highly functional dystrophin molecule whose reduced size renders it an attractive candidate for development as a therapeutic gene transfer reagent.
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PMID:Human dystrophin expression corrects the myopathic phenotype in transgenic mdx mice. 130 Nov 34

Two cases of childhood muscular dystrophy are described. One of them had clinical features suggestive of Emery-Dreifuss muscular dystrophy and the other with some features of Prader-Willi syndrome, besides proximal muscle weakness. Muscle biopsy from both cases revealed a clear abnormality of dystrophin, and were diagnosed as having Duchenne muscular dystrophy (DMD) by immunofluorescence examination; that is, absent dystrophin at the membrane of the muscle fibers. The clinical spectrum of DMD-related myopathies and the importance of dystrophin testing in childhood muscular dystrophies is discussed.
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PMID:Dystrophin test in differential diagnosis of childhood muscular dystrophies. 130 19

Duchenne's muscular dystrophy (DMD), which affects 1/3500 live male births, involves a progressive degeneration of skeletal and cardiac muscle, leading to early death. The protein dystrophin is lacking in DMD and present, but defective, in the allelic, less severe, Becker muscular dystrophy and is also missing in the mdx mouse. Experiments on the mdx mouse have suggested two possible therapies for these myopathies. Implantation of normal muscle precursor cells (mpc) into mdx skeletal muscle leads to the conversion of dystrophin-negative fibres to -positive, with consequent improvement in muscle histology. Direct injection of dystrophin cDNA into skeletal or cardiac muscle also gives rise to dystrophin-positive fibres. Although both appear promising, there are a number of questions to be answered and refinements to be made before either technique could be considered possible as treatments for myopathies in man.
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PMID:Cell transplantation and gene therapy in muscular dystrophy. 136 21

The molecular revolution that is transforming the entire biomedical field has had far-reaching impact in its application to inherited human muscle disease. The gene for Duchenne muscular dystrophy was one of the first cloned without knowledge of the defective protein product. This success was based upon the availability of key chromosomal aberrations that provided molecular landmarks for the disease locus. Subsequent discoveries regarding the mode of expression for this gene, the structure and localization of its protein product dystrophin, and molecular diagnosis of affected and carrier individuals constitute a paradigm for investigation of human genetics. Finding the gene for myotonic muscular dystrophy is requiring the brute force approach of cloning several million bases of DNA, identifying expressed sequences, and characterizing candidate genes. The gene that causes hypertrophic cardiomyopathy has been found serendipitously to be one of the genetic markers on chromosome 14, the beta myosin heavy chain.
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PMID:Molecular biology of human muscle disease. 136 10

X-linked recessive Duchenne muscular dystrophy (DMD) is caused by the absence of dystrophin, a membrane cytoskeletal protein. Dystrophin is associated with a large oligomeric complex of sarcolemmal glycoprotein. The dystrophin-glycoprotein complex has been proposed to span the sarcolemma to provide a link between the subsarcolemmal cytoskeleton and the extracellular matrix component, laminin. In DMD, the absence of dystrophin leads to a large reduction in all of the dystrophin-associated protein. We have investigated the possibility that a deficiency of a dystrophin-associated protein could be the cause of severe childhood autosomal recessive muscular dystrophy (SCARMD) with a DMD-like phenotype. Here we report the specific deficiency of the 50K dystrophin-associated glycoprotein (M(r) 50,000) in sarcolemma of SCARMD patients. Therefore, the loss of this glycoprotein is a common denominator of the pathological process leading to muscle cell necrosis in two forms of muscular dystrophy, DMD and SCARMD.
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PMID:Deficiency of the 50K dystrophin-associated glycoprotein in severe childhood autosomal recessive muscular dystrophy. 140 35

We present two cases of autosomal dominant limb girdle muscular dystrophy in a father and son. Both presented in childhood with a classical Becker muscular dystrophy phenotype. The father had initially been informed that he would not have affected children. After the diagnosis of muscular dystrophy in the son, immunoblot analysis was performed on muscle and revealed normal dystrophin. The polymerase chain reaction did not show any deletions in the dystrophin gene, and the father's dystrophin gene was not passed to his son. These cases demonstrate that autosomal dominant muscular dystrophy may present in childhood, and that dystrophin and molecular genetic analyses should be performed when considering the diagnosis of childhood muscular dystrophy, even in the presence of a classical phenotype.
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PMID:Early onset autosomal dominant progressive muscular dystrophy presenting in childhood as a Becker phenotype--the importance of dystrophin and molecular genetic analysis. 142 99

A 35-year-old man with severe progressive dilating cardiomyopathy and no clinical signs of muscle disease underwent muscular investigations because of markedly increased serum creatine kinase. Muscle biopsy demonstrated Becker type muscular dystrophy with dystrophin of low molecular weight. Genetic analysis showed a deletion spanning from exon 45 to exon 46 in the Xp21 region. Xp21 Becker type muscular dystrophy must be considered in the differential diagnosis of dilating cardiomyopathy.
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PMID:Dilating cardiomyopathy as the expression of Xp21 Becker type muscular dystrophy. 143 89

Two patients with Xp21 muscular dystrophy Becker type showed absence of dystrophin in muscle biopsy tested with 4 antibodies (polyclonal anti-60 kDa, monoclonal against the rod domain, the C-terminus and the N-terminus). DNA analysis did not detect any deletion in one patient and demonstrated deletion of exons 3-7 in the other. The cases represent an exception to the strict correlation between the dystrophin pattern in muscle biopsy and the clinical course of the disease: in fact both the patients are still walking at 14 and 15 years respectively. The possibility of similar cases must be considered not only in the prognosis of Xp21 muscular dystrophy but the more so in the evaluation of therapeutical trials.
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PMID:Absence of dystrophin in two patients with Becker type Xp21 muscular dystrophy. 148 Mar 20

We have investigated over 100 patients with Xp21 muscular dystrophy, drawing together the results of detailed clinical, genetic and dystrophin investigations. A spectrum of disease severity was confirmed, with the most homogeneous clinical groups being at either end of the spectrum, represented by the typical Duchenne and Becker phenotypes. The groups in between showed clinical heterogeneity, and variability in the genetic and dystrophin results. While an out-of-frame deletion in association with undetectable dystrophin is most likely to predict the most severe phenotype, and increasing abundance of dystrophin is associated generally with a milder clinical course, no value of dystrophin abundance reliably predicts a particular phenotype. However, deletions of the dystrophin gene involving exons 45-47 and 45-48 especially do seem to be consistently associated with the mildest Becker phenotype. Additional factors must play a role in determining the exact clinical course.
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PMID:Genetic and clinical correlations of Xp21 muscular dystrophy. 152 16


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