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

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

Duchenne's muscular dystrophy (DMD) is caused by the absence or drastic decrease of the structural protein, dystrophin, and is characterized by sarcolemmal lesions in skeletal muscle due to the stress of contraction. Dystrophin has been localized to the sarcolemma, but its organization there is not known. We report immunofluorescence studies which show that dystrophin is concentrated, along with the major muscle isoform of beta-spectrin, in three distinct domains at the sarcolemma: in elements overlying both I bands and M lines, and in occasional strands running along the longitudinal axis of the myofiber. Vinculin, which has previously been found at the sarcolemma overlying the I bands and in longitudinal strands, was present in the same three structures as spectrin and dystrophin. Controls demonstrated that the labeling was intracellular. Comparison to labeling of the lipid bilayer and of the extracellular matrix showed that the labeling for spectrin and dystrophin is associated with the intact sarcolemma and is not a result of processing artifacts. Dystrophin is not required for this lattice-like organization, as similar domains containing spectrin but not dystrophin are present in muscle from the mdx mouse and from humans with Duchenne's muscular dystrophy. We discuss the possibility that dystrophin and spectrin, along with vinculin, may function to link the contractile apparatus to the sarcolemma of normal skeletal muscle.
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PMID:Dystrophin colocalizes with beta-spectrin in distinct subsarcolemmal domains in mammalian skeletal muscle. 157 72

Using immunocytochemical methods, we examined the intensity and distribution of dystrophin and spectrin immunostaining of skeletal muscles from 51 congenital muscular dystrophy (CMD) patients including 36 Fukuyama congenital muscular dystrophy (FCMD) and 15 non-FCMD (other CMD). 17 age-matched spinal muscular atrophy (SMA) and 5 Duchenne muscular dystrophy (DMD) patient biopsies were studied as controls. All 15 non-FCMD and SMA patients showed normal localization of dystrophin at the surface membrane of each muscle fiber which was undetectable in DMD. In contrast, 34 of 36 FCMD patients exhibited an unusual immunostaining pattern with occasional (17-43%; mean = 28) negative or abnormally immunoreacted (partially deficient, fluffy or intense) fibers for dystrophin. Dystrophin was absent in 2 of 36 patients having a clinical diagnosis of FCMD, and intragenic deletion of the DMD gene was detected in one. Spectrin, a membrane cytoskeletal protein related to dystrophin, also showed an increased number of abnormally immunostained fibers in FCMD (25%), but not so high in age-matched DMD (9%) or SMA patient muscle (0%). Thus, our results suggested the presence of intrinsic factor(s) that produce abnormality of the plasma membrane of FCMD muscle.
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PMID:Immunocytochemical analysis of dystrophin in congenital muscular dystrophy. 179 74

Dystrophin, the protein product of the Duchenne muscular dystrophy locus, is encoded by a 14 kb transcript of over 65 exons. A point mutation in the homologous mouse gene causes muscular dystrophy in mdx mice. We have examined the developmental regulation of transcription of this gene in skeletal mouse muscle and also the tissue specificity of the transcript in muscle and brain, by using the polymerase chain reaction to amplify overlapping segments of dystrophin mRNA spanning the entire coding sequence and 5'-untranslated region. We have characterised a specific embryonic transcript that would encode dystrophin with a different C-terminus and have shown that this persists from the earliest stages to the adult in mdx skeletal muscle. The brain transcript shows striking sequence homology to rat and human, being highly conserved at the 5'-untranslated region and is present in both wild-type and mdx mice.
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PMID:Developmental and tissue-specific regulation of mouse dystrophin: the embryonic isoform in muscular dystrophy. 182 83

Dystrophin Related Protein is the recently identified protein product of a large autosomal transcript, showing significant similarity to dystrophin at the carboxyl terminus. Dystrophin related protein and dystrophin share a similar abundance and molecular weight, however, they differ both in their tissue distribution and expression in Duchenne/Becker muscular dystrophy. Here we define the immunolocalization of dystrophin related protein to neuromuscular and myotendinous junctions, along with peripheral nerves and vasculature of skeletal muscle. Groups of regenerating muscle fibres as well as embryonic and neonatal muscle express far greater amounts of dystrophin related protein compared with adult mdx mice. These findings may explain the paradoxical labelling seen using dystrophin antibodies in Duchenne patients and dystrophin deficient mdx mice. Finally, no abnormalities of dystrophin related protein expression were detected in three patients with Duchenne-like autosomal recessive muscular dystrophy.
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PMID:Immunolocalization and developmental expression of dystrophin related protein in skeletal muscle. 182 93

Dystrophin is the gene product of the Duchenne (DMD) and Becker (BMD) muscular dystrophy gene locus on the short arm of the X chromosome. Complete lack of dystrophin is pathognomonic for DMD and variable changes of the molecule may be observed in the milder allelic form of BMD. In the present study the two methods available for dystrophin assessment, immunofluorescence detections on cryosections (IF) and Western blotting (WB) were systematically compared using polyclonal and monoclonal antibodies to various regions along the dystrophin molecule. A total of 95 patients with DMD or BMD were investigated including two female patients. Dystrophin assessment revealed abnormal abundance and/or distribution in all 95 patients with DMD or BMD. Only trace amounts of dystrophin were detected in 29% of the DMD patients and complete lack of dystrophin was found in 71%. In two females with DMD but with normal karyotype single dystrophin-positive fibres were found among more than 90% negative fibres. Out of 26 patients with BMD 19 (73%) had a dystrophin molecule of abnormal molecular weight. The results of IF were largely compatible with those from WB but differences were also observed, e.g. one barely symptomatic BMD patient with dystrophin of increased molecular weight showed normal IF. Out of four carriers of BMD three showed evidence of reduced dystrophin immunostaining in some muscle fibres. In 20 other patients limb girdle muscualar dystrophy with "Duchenne-like" or "Becker-like" phenotype was suspected because dystrophin showed normal abundance and distribution. Focal discontinuity of muscle cell-surface dystrophin staining was observed in one patient with a congenital, autosomal recessive muscular dystrophy and in one out of five patients with polymyositis/dermatomyositis. The study emphasizes the need for, and value of, dystrophin assessment in every case of suspected BMD or DMD.
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PMID:Dystrophin as a diagnostic marker in Duchenne and Becker muscular dystrophy. Correlation of immunofluorescence and western blot. 194 22

We report an isolated case of a girl aged three years six months with Duchenne muscular dystrophy. Analysis of the patient's DNA with a probe covering the DNA gene revealed no deletion. Dystrophin, studied in biopsied muscle from the patient, using antidystrophin antibody in combination with immunofluorescence, was nearly completely absent. In this sporadic case of female muscular dystrophy, the identification of dystrophin-deficient muscle fibers made it possible to establish an accurate diagnosis of DMD affected female.
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PMID:Duchenne muscular dystrophy in a girl identified by dystrophin deficiency. 194 23

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive disorder of muscle in children, with an incidence of approximately 1 in 3,300 male births. In about a third of affected boys, the disease is due to a new mutation, and most patients die in their early 20s. Over the last few years, the genetic, biochemical and histopathological basis of DMD has been elucidated greatly. In particular, the discovery of "dystrophin," the protein product of the DMD gene is truly an epoch-making success in the history of muscular dystrophy research. Dystrophin is now thought to be a cytoskeletal protein underlying the plasma membrane (known in muscle as the sarcolemma) of normal muscle fiber, and is undetectable or greatly reduced in DMD. In this review article, dystrophin in normal skeletal muscle and various neuromuscular diseases including DMD/BMD (Becker muscular dystrophy), and its carrier is discussed.
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PMID:Dystrophin abnormality in progressive muscular dystrophy--a review article. 195 48

Dystrophin, the protein encoded by the Duchenne muscular dystrophy (DMD) gene, exists in a large oligomeric complex. We show here that four glycoproteins are integral components of the dystrophin complex and that the concentration of one of these is greatly reduced in DMD patients. Thus, the absence of dystrophin may lead to the loss of a dystrophin-associated glycoprotein, and the reduction in this glycoprotein may be one of the first stages of the molecular pathogenesis of muscular dystrophy.
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PMID:Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle. 218 35

We report 2 patients with childhood autosomal recessive muscular dystrophy. Both patients had slight muscle weakness without enlargement of the calf muscles or involvement of the facial muscles. Their clinical courses are static. Muscle histology revealed characteristic features of muscular dystrophy. Dystrophin was identifiable in the sarcolemma of both patients by immunocytochemical staining with an antidystrophin antibody. At an early age, immunocytochemical analysis with antidystrophin antibody was useful in distinguishing between childhood autosomal recessive and Duchenne muscular dystrophies.
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PMID:Dystrophin analysis in the differential diagnosis of autosomal recessive muscular dystrophy of childhood and Duchenne muscular dystrophy. 220 59


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