Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dystrophin is associated with several novel sarcolemmal proteins, including a laminin-binding extracellular glycoprotein of 156 kD (alpha-dystroglycan) and a transmembrane glycoprotein of 50 kD (adhalin). Deficiency of adhalin characterizes a severe autosomal recessive muscular dystrophy prevalent in Arabs. Here we report for the first time two mongoloid (Japanese) patients with autosomal recessive muscular dystrophy deficient in adhalin. Interestingly, adhalin was not completely absent and was faintly detectable in a patchy distribution along the sarcolemma in our patients. Although the M and B2 subunits of laminin were preserved, the B1 subunit was greatly reduced in the basal lamina surrounding muscle fibers. Our results raise a possibility that the deficiency of adhalin may be associated with the disturbance of sarcolemma-extracellular matrix interaction leading to sarcolemmal instability.
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PMID:Abnormal expression of laminin suggests disturbance of sarcolemma-extracellular matrix interaction in Japanese patients with autosomal recessive muscular dystrophy deficient in adhalin. 804 Mar 15

The absence of dystrophin causes Duchenne muscular dystrophy. Dystrophin is associated with a large complex of sarcolemmal glycoproteins which provides a linkage to the extracellular matrix component, laminin, and when dystrophin is absent all the dystrophin-associated proteins are much reduced. We report here that dystrophin-associated proteins have abnormally low expression in Fukuyama-type congenital muscular dystrophy (FCMD), despite near-normal expression of dystrophin. An abnormality of dystrophin-associated proteins in the sarcolemma seems to be a common denominator in the pathological processes leading to muscle cell necrosis in three forms of severe muscular dystrophy (Duchenne, Japanese Fukuyama-type, and north African Duchenne-like autosomal recessive).
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PMID:Abnormal expression of dystrophin-associated proteins in Fukuyama-type congenital muscular dystrophy. 810 57

To determine if dystrophin and dystrophin-associated glycoproteins (DAGs) are involved in muscle fiber necrosis in the dystrophic hamster, we examined NSJ-my/my (homozygous dystrophic) hamsters introduced from the BIO14.6 strain, by immunohistochemical and immunoblotting methods. Antibodies against dystrophin, utrophin and DAGs including 50DAG (A2), 43DAG (A3a) and 35DAG (A4) were employed for the examination. Dystrophin was stained strongly and utrophin stained very faintly along the sarcolemma of the dystrophic hamster, similar to the control. On the other hand, in the dystrophic hamster 50DAG (A2) and 35DAG (A4) were selectively defective, and 43DAG (A3a) was also decreased, although to a lesser degree. Since these results were almost identical to those seen in severe childhood autosomal recessive muscular dystrophy (SCARMD), the dystrophic hamster appears to be an animal model of SCARMD in which defects in DAGs may result in muscle fiber necrosis despite normal dystrophin expression.
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PMID:Selective defect in dystrophin-associated glycoproteins 50DAG (A2) and 35DAG (A4) in the dystrophic hamster: an animal model for severe childhood autosomal recessive muscular dystrophy (SCARMD). 817 51

Seventy-five consecutive pediatric muscular dystrophy (MD) cases were analyzed by dystrophin immunohistochemistry (75/75), Western blot analysis (26/75), DNA analysis (30/75), and immune electron microscopy (8/75). The patients included 64 males and 11 females and the clinical diagnoses were Duchenne MD (DMD) (41), Becker MD (BMD) (8), intermediate/outlier MD (4), female DMD (3), limb girdle or Becker (1), congenital MD (CMD) (10), Fukuyama CMD (1), facioscapulohumeral MD (FSH) (3), limb girdle MD (2), and other uncharacterized dystrophies (2). Dystrophin analysis was performed on all cases using the N- and C-terminal antidystrophin antibodies. Dystrophin analysis helped to exclude an Xp21 dystrophy in four patients. Except for two patients who showed normal staining with the N-terminal and abnormal staining with the C-terminal antibody, all DMD cases showed absent staining except for the immunoreactive revertant fibers, which were generally under 5%. A variety of staining patterns was seen in BMD, ranging from normal to abnormal (variable intensity of staining, partially stained/unstained fibers). Abnormalities were observed with the C-terminal antibody in one case of CMD and Fukuyama CMD, and normal staining was present in the other dystrophies. Immune electron microscopy confirmed absence of staining in DMD and normal membrane staining in other dystrophies. Our study underscores the importance of using antibodies with specificities to different regions of the dystrophin molecule for accurate diagnosis. As abnormal staining may be encountered in non-Xp21 dystrophies such as CMD, dystrophin staining should not be used in isolation to make a diagnosis of a dystrophinopathy.
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PMID:Dystrophin analysis in the diagnosis of childhood muscular dystrophy: an immunohistochemical study of 75 cases. 824 61

Two patients with slowly progressive muscle atrophy limited to only one leg are reported. They had pes equinovarus deformity and muscle weakness in the affected leg but no symptom in the other limbs. Muscle biopsies from the affected leg showed dystrophic changes consisting of variation in muscle fiber size, endomysial fibrosis, and necrotic and regenerating fibers. Dystrophin was normally expressed at the surface membrane of the muscle fibers. These two patients possibly had a variant of distal muscular dystrophy, though a neural influence could not be completely excluded.
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PMID:Monomelic muscle atrophy. 826 28

Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene, is a cytoskeletal protein tightly associated with a large oligomeric complex of sarcolemmal glycoproteins including dystroglycan, which provides a linkage to the extracellular matrix component, laminin. In DMD, the absence of dystrophin leads to a drastic reduction in all of the dystrophin-associated proteins, causing the disruption of the linkage between the subsarcolemmal cytoskeleton and the extracellular matrix which, in turn, may render muscle cells susceptible to necrosis. The COOH-terminal domains (cysteine-rich and carboxyl-terminal) of dystrophin have been suggested to interact with the sarcolemmal glycoprotein complex. However, truncated dystrophin lacking these domains was reported to be localized to the sarcolemma in four DMD patients recently. Here we report that all of the dystrophin-associated proteins are drastically reduced in the sarcolemma of three DMD patients in whom dystrophin lacking the COOH-terminal domains was properly localized to the sarcolemma. Our results indicate that the COOH-terminal domains of dystrophin are required for the proper interaction of dystrophin with the dystrophin-associated proteins and also support our hypothesis that the loss of the dystrophin-associated proteins in the sarcolemma leads to severe muscular dystrophy even when truncated dystrophin is present in the subsarcolemmal cytoskeleton.
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PMID:Deficiency of dystrophin-associated proteins in Duchenne muscular dystrophy patients lacking COOH-terminal domains of dystrophin. 834 21

During the past year significant progress has been made in understanding how dystrophin deficiency leads to muscle cell necrosis in Duchenne muscular dystrophy and Becker muscular dystrophy. Dystrophin interacts with a glycoprotein complex spanning the muscle sarcolemma, effectively linking the actin cytoskeleton to the extracellular matrix. The carboxyl terminus of dystrophin is required for glycoprotein binding. Interestingly, at least three mRNAs transcribed from the distal end of the DMD gene in tissues other than muscle have been shown to encode this domain. Deficiency of a second component of the dystrophin-associated glycoprotein complex has been shown to occur in another muscle-wasting disorder, severe childhood autosomal recessive muscular dystrophy. Sequence analysis of the entire cDNA for the autosomal dystrophin-related protein utrophin has shown that dystrophin and utrophin are closely related. Furthermore, both of these proteins have been shown to bind to the same or a similar glycoprotein complex in muscle.
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PMID:Dystrophin and related proteins. 835 25

Dystrophin is a large cytoskeletal protein encoded by the Duchenne muscular dystrophy (DMD) gene. Dystrophin is associated with a large oligomeric complex of sarcolemmal glycoproteins, including the novel laminin-binding glycoprotein called dystroglycan, which provides a linkage to the extracellular matrix. In DMD, the absence of dystrophin leads to a drastic reduction in all of the dystrophin-associated proteins. In severe childhood autosomal recessive muscular dystrophy with DMD-like phenotype (SCARMD), a specific deficiency of the 50 kDa dystrophin-associated glycoprotein is found. Thus, the disruption/dysfunction of the dystrophin-glycoprotein complex due to the deficiency of one or more of the dystrophin-associated proteins is presumed to cause the disruption of the linkage between the subsarcolemmal cytoskeleton and the extracellular matrix. This may render muscle cells susceptible to necrosis in two forms of severe childhood muscular dystrophy, DMD and SCARMD.
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PMID:Deficiency of dystrophin-associated proteins: a common mechanism leading to muscle cell necrosis in severe childhood muscular dystrophies. 835 36

Ten females presenting with muscle weakness and a raised serum creatine kinase revealed abnormalities in the expression of dystrophin in their muscle biopsies and were diagnosed as manifesting carriers of Xp21 Duchenne/Becker muscular dystrophy. Seven cases, aged 3-22 yr at the time of biopsy, had a variable proportion of dystrophin-deficient fibres and an abnormal expression on immunoblot. These were confidently diagnosed as manifesting carriers. Results in the remaining three cases, aged 8-10 yr, were less clear-cut. Dystrophin expression on immunoblots was slightly reduced and some unevenness and reduction of immunolabelling was seen on sections, but dystrophin-deficient fibres were not a feature of these cases. The weakness in the ten carriers ranged from minimal to severe and there was no correlation between the degree of weakness and the number of dystrophin-deficient fibres. Two minimally weak girls had a high proportion of dystrophin-deficient fibres. Our results show that analysis of dystrophin expression is useful for the differential diagnosis of carriers of Xp21 dystrophy and autosomal muscular dystrophy, but that dystrophin expression does not correlate directly with the degree of clinical weakness.
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PMID:Manifesting carriers of Xp21 muscular dystrophy; lack of correlation between dystrophin expression and clinical weakness. 835 39

Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene, was studied in 19 patients with Xp21 disorders and in 25 individuals with non-Xp21 muscular dystrophy. Antibodies raised to seven different regions spanning most of the protein were used for immunocytochemistry. In all patients specific dystrophin staining anomalies were detected and correlated with clinical severity and also gene deletion. In patients with Becker muscular dystrophy (BMD) the anomalies detected ranged from inter- and intra-fibre variation in labelling intensity with the same antibody or several antibodies to general reduction in staining and discontinuous staining. In vitro evidence of abnormal dystrophin breakdown was observed reanalysing the muscle of patients, with BMD and not that of non-Xp21 dystrophies, after it has been stored for several months. A number of patients with DMD showed some staining but this did not represent a diagnostic problem. Based on the data presented, it was concluded that immunocytochemistry is a powerful technique in the prognostic diagnosis of Xp21 muscular dystrophies.
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PMID:Dystrophin analysis using a panel of anti-dystrophin antibodies in Duchenne and Becker muscular dystrophy. 841 21


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