Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Duchenne muscular dystrophy (DMD), the commonest X-linked disorder, is a progressive, eventually fatal disease. With the advent of molecular genetics, the Duchenne gene and its protein product, dystrophin, have been characterised. Molecular diagnosis of DMD, identification of carriers and antenatal diagnosis are now possible. We describe here the use, in a Malaysian boy with DMD, of a recent innovation, multiplex polymerase chain reaction (PCR), to obtain molecular diagnosis by detection of dystrophin gene deletions.
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PMID:Detection of gene deletions by PCR analysis in a Malaysian patient with Duchenne muscular dystrophy. 834 Nov 71

The X-linked gene responsible for Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) encodes dystrophin, a high-molecular-weight cytoskeletal protein. The identification of the dystrophin gene through positional cloning, and the subsequent description of its protein product have opened several new fields of research and genetic diagnosis. Studies in our laboratory revealed that 26 out of 47 (55%) cases of DMD and nine out of 12 (75%) cases of BMD exhibited genomic deletion. The DMD phenotype is associated with mutations that shift the reading frame of the message, whereas the BMD phenotype is associated with mutations that maintain the reading frame. Immunofluorescence microscopy has established dystrophin's distribution on the plasma membrane of muscles. DMD patients demonstrate a lack of dystrophin on their muscle cell membrane, whereas BMD patients produce a limited amount of protein or abnormally sized protein. Extensive studies on dystrophin and the gene may lead to an understanding of the cause for this and may allow development of a rational treatment for DMD to be developed.
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PMID:[Molecular genetics of Duchenne/Becker muscular dystrophy]. 841 23

Polyclonal antibodies against the carboxy-terminal portion of dystrophin-related protein (DRP), the putative autosomal gene product which shares sequence homology with dystrophin, show the clear expression of DRP in mouse fetal muscle and in cultured human muscle cells, but not in mature mouse or human muscle. DRP has the same molecular mass as X-linked dystrophin and is recovered from the membrane fraction, but is associated with membranes more loosely than dystrophin.
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PMID:Immunoblot analysis of dystrophin-related protein (DRP). 842 31

The dystrophin-deficient, X-linked dystrophic mouse (mdx) was used to evaluate the efficacy of prednisolone treatment. A test protocol was used to take advantage of the quantifiable weakness and disability as well as molecular genetic defect shared with the X-linked Duchenne muscular dystrophy (DMD). Whole-body weakness and fatigue were determined by non-invasive force-transducer physiographic and variable-speed treadmill techniques, respectively. Other measurements included hind-limb muscle protein, calcium, and histomorphology. Subcutaneously-administered prednisolone elicited significant improvements in whole body strength throughout a two-month test period. Increases in strength were also accompanied by measurable increments in running endurance. In fact, prednisolone treatment appeared to protect mdx mice from the stressful effect of continuous running as determined by strength and muscle fiber diameter. Test results from this study support the limited therapeutic benefit observed previously in DMD patients treated with the glucocorticoid.
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PMID:Strength and endurance in the therapeutic evaluation of prednisolone-treated MDX mice. 843 32

We have investigated 67 patients with proven Becker muscular dystrophy (BMD) using a standard protocol including a detailed history and a functional and clinical examination. Our aim was to define the natural history of the disease in a large cohort of patients in the light of the diagnostic methods now available. In all patients with or without an X-linked family history, the diagnosis was confirmed by the identification of a deletion or other abnormality in the dystrophin gene, and abnormal dystrophin on immunoblotting and immunocytochemistry of muscle biopsy samples. In graphs of functional and muscle score against age, two groups of patients emerged. In the larger group the disease was milder and patients remained ambulant into their forties or beyond. A smaller group had more severe disease with a slightly earlier onset, much earlier loss of ambulation, more frequent abnormal electrocardiographic findings and much lower reproductive fitness. The relationship of these clinical findings to the genetic and protein abnormalities found in the patients is explored in the accompanying paper.
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PMID:The clinical, genetic and dystrophin characteristics of Becker muscular dystrophy. I. Natural history. 843 27

Duchenne progressive muscular dystrophy is a lethal and common X-linked genetic disease caused by the absence of dystrophin, a 427K protein encoded by a 14 kilobase transcript. Two approaches have been proposed to correct the dystrophin deficiency in muscle. The first, myoblast transfer therapy, uses cells from normal donors, whereas the second involves direct intramuscular injection of recombinant plasmids expressing dystrophin. Adenovirus is an efficient vector for in vivo expression of various foreign genes. It has recently been demonstrated that a recombinant adenovirus expressing the lac-Z reporter gene can infect stably many mouse tissues, particularly muscle and heart. We have tested the ability of a recombinant adenovirus, containing a 6.3 kilobase pair Becker-like dystrophin complementary DNA driven by the Rous sarcoma virus promoter to direct the expression of a 'minidystrophin' in infected 293 cells and C2 myoblasts, and in the mdx mouse, after intramuscular injection. We report here that in vivo, we have obtained a sarcolemmal immunostaining in up to 50% of fibres of the injected muscle.
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PMID:Efficient adenovirus-mediated transfer of a human minidystrophin gene to skeletal muscle of mdx mice. 843 25

Identification of the defective gene and the absent gene product dystrophin can substantiate the clinical evidence for manifesting X-linked Duchenne type muscular dystrophy (DMD). It is not always possible, however, to rule out definitely a clinically asymptomatic carrier status in question, since even in the proven carrier DNA analysis is often inconclusive, and multinucleated skeletal muscle fibers express a basically normal membrane dystrophin. To substantiate the value of endomyocardial biopsy as a new tool for detection of the DMD carrier status we examined an endomyocardial biopsy of a volunteer who met the clinical criteria of a DMD carrier. Dystrophin immunohistochemistry and western blot of her skeletal muscle biopsy were inconclusive, and polymerase chain reaction and cDNA analysis failed to locate directly the X-chromosomal defect. We observed a clearcut mosaic of dystrophin-positive and -negative mononucleated cardiac muscle cells, reflecting a heterozygote carrier status in her endomyocardial biopsy, whereas 20 controls were uniformely positive. The incidence of DMD (1:3000 males) and especially the 30% spontaneous mutation rate, still the major pitfall in DNA analysis, show the need for an additional diagnostic tool.
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PMID:Heterozygotic gene expression in endomyocardial biopsies: a new diagnostic tool confirms the Duchenne carrier status. 848 29

Duchenne's muscular dystrophy (DMD) is a common X-linked neuromuscular disease which predominantly affects skeletal and cardiac muscle. The absence of dystrophin, the metabolic defect that causes DMD, leads to a peculiar cardiomyopathy which initially affects the posterior wall of the left ventricle. We review evidence that dystrophin deficient myocytes become dystrophic in order of increasing axial stress upon the myocyte. Thus, dystrophin's function may be that of physically reinforcing the sarcolemma against the axial forces exerted upon the myocyte.
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PMID:The cardiomyopathy of Duchenne's muscular dystrophy and the function of dystrophin. 850 96

A mild non-progressive cognitive defect is a feature of the fatal X-linked disease, Duchenne muscular dystrophy. Recent studies have identified the genetic defect and the resulting loss of the protein dystrophin, and shown that dystrophin messenger RNA and protein are present in normal brain tissue. We have performed western immunoblotting and fluorescence immunocytochemistry using a sensitive antibody made against a large fragment of the dystrophin molecule to study the regional, cellular and subcellular distribution of dystrophin in the mammalian brain. The brains of B10 (control) and mdx (dystrophin deficient null mutant) mouse brain were compared on a point-by-point basis to verify that only dystrophin and not autosomal dystrophin related protein or cross-reacting proteins were being identified. In addition three murine neurologic mutants, nervous, lurcher, and weaver, were studied to refine the localization of dystrophin. In western immunoblots, dystrophin is present in all regions of the brain and in greatest abundance in the cerebellum. Dystrophin, as demonstrated in immunofluorescence, is present in neurons, but not in glia or myelin, and forms punctate foci associated with the plasma membrane of perikarya and dendrites, but not axons. While dystrophin is abundant in cerebral cortical neurons and cerebellar Purkinje cells, it is absent from most subcortical neurons, the granule cells of fascia dentata, and cerebellar neurons other than Purkinje cells. The absence of dystrophin in the cerebellum of the Purkinje cell deficient mutants nervous and lurcher, and its presence in the granule cell deficient mutant weaver indicate that dystrophin is a component of Purkinje cells rather than closely apposed afferents to those cells. The distribution and localization of dystrophin suggests a role in organizing the plasma membrane, possibly as an anchor of the postsynaptic apparatus, a possible basis for the cognitive defect in Duchenne dystrophy.
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PMID:The distribution of dystrophin in the murine central nervous system: an immunocytochemical study. 851 41

X-linked Duchenne muscular dystrophy (DMD) is frequently associated with a nonprogressive, cognitive defect attributed to the absence of dystrophin in the brain of DMD patients. The mutant mdx mouse, lacking in 427-kDa dystrophin in both muscle and brain tissues, is considered to be a valuable model of human DMD. In the present study, we compared mdx and C57BL/10 control mice and showed that mdx mice had impaired retention in a T-maze, delayed spontaneous alternation task 24 h, but not 6 h, after acquisition. mdx mice were not impaired in acquisition of a bar-pressing task on 4 consecutive days but showed poor retention 22 days after the last training session. Mutants and controls showed similar behavioral responses in free exploration and light/dark choice situations and did not differ in spontaneous locomotor activity or motor coordination. Retention impairments at long delays in mdx mice suggest a role of dystrophin in long-term consolidation processes.
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PMID:Influence of dystrophin-gene mutation on mdx mouse behavior. I. Retention deficits at long delays in spontaneous alternation and bar-pressing tasks. 854 Aug 95


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