Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0235394 (wasting)
 8,040 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Duchenne muscular dystrophy (DMD) is a human X-linked biochemical defect resulting in the progressive wasting of skeletal muscle of affected individuals. It is the most common and is considered to be the most devastating of the muscular dystrophies, affecting about 1 in 3,500 live-born males. The gene that, when defective, results in this disorder was recently isolated. Using the cloned complementary DNA sequences corresponding to the DMD gene, antibodies have been produced that react with a protein species of relative molecular mass (Mr) approximately 400,000 (400K) which was absent in two DMD-affected individuals and in mdx mice. This protein species is called dystrophin because of its identification by molecular-genetic analysis of affected individuals. Here we show that dystrophin is associated with the triadic junctions in skeletal muscle, and is therefore probably involved with Ca2+ homoeostasis. We also show that the approximately 450K ryanodine receptor/sarcoplasmic reticulum Ca2+ channel, which has the large size and subcellular distribution characteristics of dystrophin, is an immunologically distinct protein species.
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PMID:Subcellular fractionation of dystrophin to the triads of skeletal muscle. 244 3

Duchenne muscular dystrophy (DMD) and its less severe allele Becker muscular dystrophy (BMD) are progressive muscle-wasting disorders of children. DMD is characterized by rapid loss of muscle fibres and the ensuing weakness results in lost mobility and eventual premature death. Despite extensive research for many years, the basic underlying biochemical defect has remained elusive. Here I try to demonstrate how the powerful techniques of molecular genetics can be used to gain a further understanding of this particular disorder and how, in principle, the techniques can be applied to the other 3000 human genetic disorders that are so far uncharacterized. Once the chromosomal map position of DMD was established, the locus that was being disrupted by mutation could be identified and the encoded protein product predicted from the nucleotide sequence of the RNA transcript. This has led to the identification of a previously uncharacterized protein named dystrophin. As the normal function of dystrophin is determined, more accurate clinical diagnosis of DMD and BMD should result and potential approaches to therapy should be designed.
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PMID:The Wellcome lecture, 1988. Muscular dystrophy: a time of hope. 256 97

Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disorder affecting 1 in 3500 males. A less severe and less common form is Becker muscular dystrophy (BMD). Only recently has the basic defect in DMD and BMD been recognized: a region on the human X chromosome is disrupted by mutation. The primary transcript of the region was detected, and cDNA clones were isolated that encompassed the entire transcript. The sequence of the encoded protein was predicted from cDNA nucleotide sequence, portions of the protein were overexpressed in bacterial cells, and these peptides were used to generate immunoreagents against the DMD gene protein, dystrophin. The molecular genetic identification of this protein via analysis of mutations found in patients' material has led to a means of improved diagnosis of DMD/BMD in affected individuals and their family members. The severely affected DMD patients have little or no detectable dystrophin in their muscle, whereas BMD patients have nearly normal concentrations of an altered form of dystrophin; patients with all other neuromuscular diseases have normal dystrophin.
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PMID:Molecular genetics of Duchenne and Becker muscular dystrophy: emphasis on improved diagnosis. 266 32

Duchenne muscular dystrophy is a severe X chromosome-linked, muscle-wasting disease caused by lack of the protein dystrophin. The exact function of dystrophin remains to be determined. However, analysis of its interaction with a large oligomeric protein complex at the sarcolemma and the identification of a structurally related protein, utrophin, is leading to the characterization of candidate genes for other neuromuscular disorders.
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PMID:Increasing complexity of the dystrophin-associated protein complex. 807 78

A 22-year-old man with Down syndrome had a history of progressive muscular wasting which began at the age of 12 years. Serum CK level was elevated to 545 U/l (normal < 150) and muscle CT scan revealed patchy low density areas in the proximal muscles. A muscle biopsy specimen revealed marked dystrophic changes with patchy immunostaining for dystrophin. Multiplex PCR analysis of the genomic DNA extracted from peripheral blood lymphocytes disclosed a deletion of exons 45-47 of the dystrophin gene, confirming a diagnosis of Becker muscular dystrophy (BMD). This is the first report of Down syndrome complicated with BMD. Careful observation is required in detecting a coexistence of myopathy in mentally retarded patients.
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PMID:[A case of Down syndrome complicated with Becker muscular dystrophy]. 812 83

The traditional clinical criteria for identifying a manifesting Duchenne carrier are a positive family history, proximal limb weakness, calf hypertrophy, high serum creatine kinase. We describe a 52-yr-old woman with history of 1 1/2 yr of progressive wasting and weakness of the left calf and marked elevation of serum creatine kinase. Although her quadriceps was clinically silent, it showed mild alterations on ultrasound, computerized tomography and biopsy, and some abnormalities in dystrophin immunostaining, suggesting a manifesting carrier of the dystrophin gene. Given the enormous variability of manifestations of the Duchenne variant in females, we suggest that great care must be exercised in ruling out this genetic disorder.
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PMID:Calf myopathy with a twist. 817 47

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

Among the diverse family of collagens, the widely expressed microfibrillar type VI collagen is believed to play a role in bridging cells with the extracellular matrix. Several observations imply substrate properties for cell attachment as well as association with major collagen fibers. Previously, we have established genetic linkage between the genes encoding the three constituent alpha-chains of type VI collagen and Bethlem myopathy. A distinctive feature of this autosomal dominant disorder consists of contractures of multiple joints in addition to generalized muscular weakness and wasting. Nine kindreds show genetic linkage to the COL6A1-COL6A2 cluster on chromosome 21q22.3 (refs 3,4; manuscript submitted) whereas one family shows linkage to markers on chromosome 2q37 close to COL6A3 (ref. 5). Sequence analysis in four families reveals a mutation in COL6A1 in one and a COL6A2 mutation in two other kindreds. Both mutations disrupt the Gly-X-Y motif of the triple helical domain by substitution of Gly for either Val or Ser. Analogous to the putative perturbation of the anchoring function of the dystrophin-associated complex in congenital muscular dystrophy with mutations in the alpha 2-subunit of laminin, our observations suggest a similar mechanism in Bethlem myopathy.
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PMID:Type VI collagen mutations in Bethlem myopathy, an autosomal dominant myopathy with contractures. 878 32

Duchenne muscular dystrophy (DMD) is a severe, progressive muscle-wasting disease that causes cardiac or respiratory failure and results in death at about 20 years of age. Replacement of the missing protein, dystrophin, using myoblast transfer in humans or viral/liposomal delivery in the mouse DMD model is inefficient and short-lived. One alternative approach to treatment would be to upregulate the closely related protein, utrophin, which might be able to compensate for the dystrophin deficiency in all relevant muscles. As a first step to this approach, we have expressed a utrophin transgene at high levels in the dystrophin-deficient mdx mouse. Our results indicate that high expression of the utrophin transgene in skeletal and diaphragm muscle can markedly reduce the dystrophic pathology. These data suggest that systemic upregulation of utrophin in DMD patients may lead to the development of an effective treatment for this devastating disorder.
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PMID:Amelioration of the dystrophic phenotype of mdx mice using a truncated utrophin transgene. 893 8

Duchenne muscular dystrophy (DMD) is a severe, progressive, X-linked muscle-wasting disorder with an incidence of approximately 1/3,500 male births. Females are also affected, in rare instances. The manifestation of mild to severe symptoms in female carriers of dystrophin mutations is often the result of the preferential inactivation of the X chromosome carrying the normal dystrophin gene. The severity of the symptoms is dependent on the proportion of cells that have inactivated the normal X chromosome. A skewed pattern of X inactivation is also responsible for the clinical manifestation of DMD in females carrying X;autosome translocations, which disrupt the dystrophin gene. DMD may also be observed in females with Turner syndrome (45,X), if the remaining X chromosome carries a DMD mutation. We report here the case of a karyotypically normal female affected with DMD as a result of homozygosity for a deletion of exon 50 of the dystrophin gene. PCR analysis of microsatellite markers spanning the length of the X chromosome demonstrated that homozygosity for the dystrophin gene mutation was caused by maternal isodisomy for the entire X chromosome. This finding demonstrates that uniparental isodisomy of the X chromosome is an additional mechanism for the expression of X-linked recessive disorders. The proband's clinical presentation is consistent with the absence of imprinted genes (i.e., genes that are selectively expressed based on the parent of origin) on the X chromosome.
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PMID:Uniparental disomy of the entire X chromosome in a female with Duchenne muscular dystrophy. 898 59


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