Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 4-year-old girl was identified with high creatine kinase (CK) values, and mild muscle weakness in a limb-girdle distribution. Results of dystrophin analysis of the muscle biopsy were consistent with a manifesting heterozygote for Duchenne muscular dystrophy. In peripheral lymphocytes she had a t(X;12) (p21.2;q24.33). Late DNA replication studies demonstrated inactivation of the normal X chromosome in 99.4% of cells. Dystrophin immunofluorescence showed 64% dystrophin-negative muscle fibers. Dystrophin content of muscle by immunoblot was approximately 5% of normal. The discordance between the percent of normal X inactivation and percent of dystrophin-negative cells may be explained by compensatory protection of dystrophin by rare nuclei with the normal X active in multi-nucleated muscle fibers with shared cytoplasm.
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PMID:X inactivation and dystrophin studies in a t(X;12) female: evidence for biochemical normalization in Duchenne muscular dystrophy carriers. 141 26

Duchenne muscular dystrophy (DMD) is an X-linked disease characterized by progressive muscle weakness and degeneration. Dystrophin is the product of the missing gene in this disorder. However, the cause of the dystrophic process is not understood. Transient muscle injury is normally seen after muscle exercise, and may be a necessary process in muscle growth and preservation. We, therefore, chose to evaluate the role of exercise in Duchenne dystrophy by studying the canine X-linked animal model (CXMD). These dogs also lack dystrophin and have clinical signs similar to humans. Exercise was initiated by electrical stimulation, and muscle metabolism was monitored with phosphorus magnetic resonance spectroscopy (P-MRS). Dogs with CXMD had abnormal muscle pathology and markedly elevated serum CK. The inorganic phosphate (Pi) to phosphocreatine (PCr) ratio was increased in CXMD dogs at rest compared with normal dogs (Pi/(Pi + PCr) = 0.166 +/- 0.054 for CXMD and 0.073 +/- 0.017 for normals, mean +/- SE). No changes in resting ATP, pH, phosphomonoesters (PME), and phosphodiesters (PDE) were seen. The mean Pi/(Pi + PCr) and pH values during stimulation were normal in the CXMD dogs. Two to three days after electrical stimulation, resting Pi/(Pi + PCr) ratios were significantly increased in the CXMD dogs (0.127 +/- 0.029 compared with 0.172 +/- 0.054, mean +/- SD). Normal dogs showed no increase in Pi/(Pi + PCr) following stimulation. There was a 50-fold greater increase in serum CK in CXMD compared with normal dogs following exercise. These results indicate greater muscle injury in CXMD muscle, and suggest that in the absence of dystrophin, exercise-induced muscle injury may play a role in the dystrophic process.
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PMID:Canine X-linked muscular dystrophy studied with in vivo phosphorus magnetic resonance spectroscopy. 174 83

A 30-year-old man showed exercise-induced myalgia, calf muscle hypertrophy and high serum creatine kinase level, without muscular weakness. The symptoms began in childhood and did not progress. Electromyographic findings were consistent with myopathy, and the muscle histology showed nonspecific myopathic changes without evidence of storage of glycogen or lipid. Immunohistochemical staining with antibodies raised against three different dystrophin peptides revealed proper subcellular localization of dystrophin at the sarcolemma of all myofibers, but the intensity of the stain was decreased. Western blot analysis using the same antibodies revealed normal dystrophin in size, but showed the reduced amount of the protein. The DNA obtained from the patient's peripheral leukocyte showed a deletion of the dystrophin gene including exon 45 by using PCR technique. Though the detailed size and portion of the deleted gene are not ascertained, the deletion in this case may not severely affect the function of dystrophin, unlike cases of Duchenne or Becker muscular dystrophy. Dystrophin analysis is useful for the etiologic diagnosis in cases of myalgia and high CKemia.
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PMID:[Exercise-induced myalgia and high CKemia with a deletion in the dystrophin gene]. 180 75

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

A 26-year-old male with "quadriceps myopathy" is presented. He had a family history and only the bilateral quadriceps were wasted, without symptomatic weakness. The specimen of the muscle biopsy showed typical myopathic features without inflammatory reactions. The patchy defect of muscular dystrophin was proved by immunohistochemical study. Dystrophin analysis revealed abnormal 380 kDa dystrophin. Gene deletion was proved at exon 45-48 of Xp21 without frameshift. This case was considered to be a clinical variant form of Becker muscular dystrophy.
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PMID:"Quadriceps myopathy": a clinical variant form of Becker muscular dystrophy. 223 Aug 47

A patient with non-Fukuyama type merosin-positive congenital muscular dystrophy (nonFCMD) who had severe muscle weakness leading to early death was reported. He was the first product of epileptic mother who had been placed on phenobarbital and phenytoin. The patient had severe respiratory failure and muscle weakness at the neonatal period, and died at 4 months of age. Multiple joint contractures were also noted at birth. Serum creatine kinase was within normal limits (123 IU/l). Electromyography showed a myogenic pattern. Brain computed tomographic (CT) scan and magnetic resonance imaging (MRI) were normal without white matter lucency or pachygyria. Muscle biopsy revealed dystrophic changes and type 2C fiber predominance. Dystrophin, dystrophin-associated glycoproteins and merosin were all positively demonstrated. Although patients with merosin-positive nonFCMD have relatively mild clinical course, our patient had severe muscle weakness with fatal outcome. Defect in muscle fiber maturation and differentiation, such as an increase of undifferentiated type 2C fibers, may be a major factor to influence muscle symptoms in non FCMD.
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PMID:[Non-Fukuyama type merosin-positive congenital muscular dystrophy with delayed muscle fiber type differentiation: a case report]. 761 93

We have previously shown in a large X-linked pedigree that a deletion removing the dystrophin muscle promoter, the first muscle exon and part of intron 1 caused a severe dilated cardiomyopathy with no associated muscle weakness. Dystrophin expression was present in the muscle of affected males and transcription studies indicated that this dystrophin originated from the brain and Purkinje cell isoforms, upregulated in this skeletal muscle. We have now studied dystrophin transcription and expression in the heart of one member of this family. In contrast to the skeletal muscle, dystrophin transcription and expression were absent in the heart, with the exception of the distal Dp71 dystrophin isoform, normally present in the heart. The 43- and 50-kD dystrophin-associated proteins were severely reduced in the heart, despite the presence of Dp71, but not in skeletal muscle. The absence of dystrophin and the down-regulation of the dystrophin-associated proteins in the heart accounted for the severe cardiomyopathy in this family. The mutation present in these males selectively affects dystrophin expression in the heart; this could be secondary to the removal of cardiac-specific regulatory sequences. This family may represent the first example of a mutation specifically affecting the cardiac expression of a gene, present physiologically in both the skeletal and cardiac muscles.
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PMID:A mutation in the dystrophin gene selectively affecting dystrophin expression in the heart. 763 62

We recently described a family where a deletion of the dystrophin gene was associated with a severe dilated cardiomyopathy without skeletal muscle weakness. The deletion removed the muscle promoter region and the first muscle exon, but not the brain or Purkinje-cell promoters. Dystrophin was detected immunocytochemically in the skeletal muscle from this family, despite the fact that the deletion eliminated the transcriptional start site of the muscle isoform. In order to determine which promoter was driving dystrophin transcription in skeletal muscle of these individuals, we first evaluated the expression of the exon 1 of muscle, brain, and Purkinje-cell isoforms in normal human skeletal and cardiac muscles and in mouse brain and cerebellum. Our data indicate that, with the exception of minimal expression of the brain isoform, only the muscle isoform is significantly transcribed in skeletal muscle, whereas both the exon 1 muscle and brain isoforms are highly expressed in cardiac muscle. In contrast to what is observed in normal muscle, the skeletal muscle of our patients showed expression of both the brain and the Purkinje-cell isoforms. The overexpression, in skeletal muscle, of these two isoforms thus appears to be of crucial importance in preventing a myopathy in these affected males. The reason for the severe cardiomyopathy remains speculative, in the absence of dystrophin data on their heart. However, we have found in the 5' end of intron 1, a region deleted in our cases, regulatory sequences that might be of importance for dystrophin expression in various tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transcription of the dystrophin gene in normal tissues and in skeletal muscle of a family with X-linked dilated cardiomyopathy. 782 71

Cardiomyopathy is often found in patients with Duchenne and Becker muscular dystrophy, which are X linked muscle diseases caused by mutations in the dystrophin gene. Dystrophin defects present in many different ways and cases of mild Becker muscular dystrophy have been described in which cardiomyopathy was severe. Female carriers of Duchenne muscular dystrophy can develop symptomatic skeletal myopathy alone or combined with dilated cardiomyopathy. They can also develop dilated cardiomyopathy alone. X linked dilated cardiomyopathy has been found in association with dystrophin defects. The relation between the molecular defects and the cardiac phenotypes has not yet been established. New mutations in the dystrophin gene are common and such mutations cause one third of the cases with Duchenne and Becker muscular dystrophy. This means that sporadic cases of cardiomyopathy caused by dystrophin defects are likely. This paper reports such a case in a boy of 14 who died of dilated cardiomyopathy. Before the cardiac investigation, which was performed one month before he died, he had not complained of muscular weakness. He had minor signs of limb girdle myopathy and slightly increased concentrations of serum creatine kinase. He was found to have an unusual deletion in the dystrophin gene.
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PMID:Dilated cardiomyopathy and the dystrophin gene: an illustrated review. 783 92

A 54-year-old farmer with a negative family history had had mild proximal weakness for the previous 4 years. Clinical examination showed marked scoliosis, barrel-shaped chest, diffuse hypotrophy, and mild proximal weakness. Creatine kinase was 938 U/l; electrocardiography and echocardiography were normal. EMG disclosed myopathic changes. Muscle biopsy showed slight, nonspecific alterations. Dystrophin was present and normally distributed with antibodies against the C-terminal and N-terminal, whereas it was not recognized by the antibody against the rod domain. Western blotting detected an abnormal molecular weight protein of 320 kd (normal, 427 kd). Southern blot analysis revealed a deletion from exon 21 to exon 44, corresponding to 26% of the coding region of dystrophin. Six years' follow-up did not disclose progression of the muscle disease.
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PMID:Unusual expression and very mild course of Xp21 muscular dystrophy (Becker type) in a 60-year-old man with 26 percent deletion of the dystrophin gene. 814 28


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