Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 33 patients suffering from the Duchenne muscular dystrophy (DMD), 7 healthy donors and a DMD risk family were studied by means of polymerase multiplex chain reaction (MPCR) with 6 oligoprimer pairs for 6 different exons of dystrophin gene. The deletions varying in sizes from 1 to 6 exons were detected in 12 out of 33 DMD patients studied (36.3%). The prenatal diagnosis of DMD was carried out by chorionic villus biopsy on the 1st trimester of pregnancy. Contrary to earlier findings, in elder brother with sever DMD manifestation, no visible deletion was detected in the DNA sample from the male foetus and thus the diagnosis of DMD in foetus was rejected. The perspectives of MPCR in pre and postnatal diagnosis of DMD are discussed.
Mol Gen Mikrobiol Virusol 1991 Sep
PMID:[Analysis of deletion mutations of the dystrophin gene by the multiplex polymerase chain reaction method in the diagnosis of Duchenne muscular dystrophy]. 174 68

Recent advances concerning the genetic and biochemical basis of Duchenne and Becker muscular dystrophies have resulted in a good understanding of the etiology of these common dystrophies. An important secondary consequence of the genetic and biochemical research has been the generation of gene-based and protein-based diagnostic tools which enable a 'molecular diagnosis' for patients and their families. This review summarizes our current understanding of the genetics, biochemistry, and pathophysiology of Duchenne dystrophy, and gives an overview of the molecular diagnostic tools and their applications. Recent correlations of clinical, genetic and biochemical data have indicated that dystrophinopathies can present with a wide range of neuromuscular symptoms, and that neither male sex nor proximal weakness are diagnostic prerequisites for consideration of an underlying dystrophin abnormality.
Mol Aspects Med 1991
PMID:Dystrophin and disease. 177 Aug 36

Routinely, we detect 0,1 pg of plasmid DNA using the nonradioactive DNA labeling and detection kit produced by Boehringer Mannheim (FRG). Using the kit we have determined the carrier status of a woman in a family with a case of Duchenne muscular dystrophy by the blot hybridization technique.
Mol Gen Mikrobiol Virusol 1991 May
PMID:[Use of nonradioactively labelled DNA-probes for DNA-diagnosis of Duchenne's muscular dystrophy]. 189 56

Duchenne muscular dystrophy carrier detection has been performed by using probes XJ1.1 (intragenic probe) and probe 754 for a girl. The carrier probability was estimated by means of a computer program GenRisk combining pedigree and DNA-probe data and turned out to be 95%.
Mol Gen Mikrobiol Virusol 1990 Dec
PMID:[DNA-diagnosis of carriers of the Duchenne muscular dystrophy gene]. 208 41

An assessment of the replicative life-span of myoblasts is of fundamental importance in designing treatment strategies for Duchenne muscular dystrophy (DMD) based on cell or gene therapy. To ascertain myoblast life-span, or the total number of cell divisions of which a myoblast was capable, we serially passaged and counted the progeny of individual myoblasts until they senesced. We compared the life-span of myoblasts from eight DMD patients with controls: three individuals with no known neuromuscular disease, three DMD carriers, and three patients with other muscle degenerative diseases. A decline in replicative capacity was observed with increasing donor age, which was markedly accelerated for DMD relative to control myoblasts. The average myoblast from a 5-year-old control was capable of 56 doublings, or a potential yield of approximately 10(17) cells per cell. By contrast, at 2 years of age, the typical age at clinical onset, only 6% of DMD myoblasts had a life-span of 50 doublings in tissue culture, and by age 7 DMD myoblasts capable of 10 doublings were rare. Our results suggest that the myoblasts (satellite cells) of even the youngest DMD patients have undergone extensive division in an attempt to regenerate degenerating myofibers. These findings have implications for therapeutic intervention in DMD involving genetic engineering and myoblast implantation.
Somat Cell Mol Genet 1990 Nov
PMID:Accelerated age-related decline in replicative life-span of Duchenne muscular dystrophy myoblasts: implications for cell and gene therapy. 226 30

Duchenne muscular dystrophy (DMD) gene transcripts are most abundant in normal skeletal and cardiac muscle and accumulate as normal myoblasts differentiate into multinucleated myotubes. In this report we describe our initial studies aimed at defining the cis-acting sequences and trans-acting factors involved in the myogenic regulation of DMD gene transcription. A cosmid clone containing the first exon of the DMD gene has been isolated, and sequences lying upstream of exon 1 were analyzed for homologies to other muscle-specific gene promoters and for their ability to direct muscle-specific transcription of chimeric chloramphenicol acetyltransferase (CAT) gene constructs. The results indicate that the transcriptional start site for this gene lies 37 base pairs (bp) upstream of the 5' end of the published cDNA sequence and that 850 bp of upstream sequence can direct CAT gene expression in a muscle-specific manner. Sequence analysis indicates that in addition to an ATA and GC box, this region contains domains that have been implicated in the regulation of other muscle-specific genes: a CArG box at -91 bp; myocyte-specific enhancer-binding nuclear factor 1 binding site homologies at -58, -535, and -583 bp; and a muscle-CAAT consensus sequence at -394 bp relative to the cap site. Our observation that only 149 bp of upstream sequence is required for muscle-specific expression of a chimeric CAT gene construct further implicates the CArG and myocyte-specific enhancer-binding nuclear factor 1 binding homologies as important domains in the regulation of this gene. On the other hand, the unique profile of myogenic cell line-specific induction displayed by our DMD promoter-CAT gene constructs suggests that other as yet undefined cis-acting sequences and/or trans-acting factors may also be involved.
Mol Cell Biol 1990 Jan
PMID:Molecular and functional analysis of the muscle-specific promoter region of the Duchenne muscular dystrophy gene. 240 34

Through a process that has come to be known as reverse genetics, the gene and gene product involved in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) have been identified. The DMD/BMD gene is over 2 million base pairs in size and over 50% of DMD/BMD patients harbor submicroscopic deletions for portions of the gene. The gene product, named dystrophin, is 400 Kd in size. Dystrophin is present in skeletal, cardiac, and smooth muscles, as well as brain. The protein is absent or altered in DMD/BMD patient muscle. The normal function of dystrophin and the reasons why its alteration results in the DMD/BMD phenotypes are presently unknown. The discoveries to date, however, provide a starting point for investigating the fundamental pathogenetic mechanisms involved in DMD/BMD.
Mol Chem Neuropathol 1989 Feb
PMID:Unraveling the mysteries of Duchenne and Becker muscular dystrophy. 266 Aug 36

The current hypothesis that the Duchenne/Becker muscular dystrophy locus encodes a single 2,000 kb gene is analyzed. The apparent encoding efficiency, the individual and total exon/intron ratios, and the heterogeneity of deletions associated with the disease, which are currently interpreted as supporting the single gene hypothesis, are also consistent with the alternative hypothesis that this locus is a portion of a complex of related gene clusters which include synthenic transcriptional units of enzymes and ligand transport proteins of one or more convergent metabolic pathways. The high recombination frequency and high rate of deletions are consistent with a locus that has recently evolved from pseudoautosomal origin. The propositions that nebulin or dystrophin is the product of the DMD locus, and that the mdx locus in the mouse is homologous to that of DMD, are critically evaluated. Several lines of evidence support the contention that developmental and tissue-specific enzymes of acyl-specific phospholipid synthesis are encoded in these clusters. Phenotypic variability not accountable for by deletion heterogeneity is postulated to arise from epistatic interactions with other loci within or outside these putative clusters. Some testable predictions of these hypotheses are suggested.
Mol Cell Biochem 1988 Jun
PMID:On the nature of the Duchenne muscular dystrophy locus: a portion of a complex of related gene clusters of recent pseudoautosomal origin? 305 Apr 49

Although muscle and nerve are reasonably well protected against active oxygen and related free radicals, environmental or inherited malfunctions can overpower their defences. Active oxygen is involved in many neuropathies and myopathies. In every case the damage is caused by agents which exert effects disproportionately greater than the quantities encountered, through a variety of amplification mechanisms. We can categorize these amplification mechanisms as follows: (a) non-replacement of targets (e.g. loss of genetic information, ataxia telangectasia being an hereditary ataxia in which an oxygen mediated chromosomal instability is apparent), (b) non-removal of unwanted materials (e.g. lipofuscin accumulation in brain and heart), (c) redox cycling, usually involving catalysis by trace-metal ions (e.g. some forms of Parkinsonism), (d) non-redox catalysis (e.g. toxicity in cardiac muscle or brain due to vanadium or aluminium respectively), (e) modification of ion transport (e.g. calcium ionophore or acrylamide induce histopathological changes in muscle, similar in some respects to those seen in Duchenne muscular dystrophy), (f) compromised defences (e.g. muscle and nerve become particularly susceptible to free radical damage after loss of the protective actions of vitamin E), and (g) amplification by inflammatory and immune responses (e.g. multiple sclerosis, reperfusion injury to brain and heart, and traumatic injury to nervous tissue). Unfortunately, a variety of therapeutic agents which might be expected to protect against almost every conceivable form of oxygen mediated damage have proved clinically ineffective in most of these disorders. The reasons for this will be explored with an emphasis on common features, differences, mechanisms, and potential therapeutic approaches.
Mol Cell Biochem 1988 Dec
PMID:Active oxygen in neuromuscular disorders. 306 22

The protein dystrophin is absent in muscles of patients with Duchenne muscular dystrophy (DMD) as well as in mdx mice. The mdx mouse diaphragm closely resembles the human DMD phenotype and should serve as an appropriate model for future studies of dystrophin gene replacement. In this regard, recombinant adenovirus (AV) holds great promise as a vector for delivering a functional dystrophin gene to muscle. However, the use of AV is hampered by the development of an immune response against transduced cells, resulting in short-lived transgene expression as well as possible adverse effects on organ function. In the present study, sensitive reporter genes were employed to determine the efficiency and functional consequences of AV-mediated gene transfer to the diaphragm in both normal and mdx adult mice. One week after direct intramuscular injection of AV into the diaphragm, the level of transgene expression was significantly increased in mdx compared with normal diaphragms. In addition, small-caliber fibers (< 500 microns2) demonstrated preferential transduction in both groups of mice. Normal diaphragms receiving AV exhibited a substantial reduction in maximal twitch and tetanic force generation, whereas no significant effect on diaphragm contractility was found in the mdx group at 1 wk after injection. At 1 mo after AV administration, however, there was a significant decrease in force production by both normal and mdx diaphragms. Immunosuppression with cyclosporine A over 1 mo did not augment the level of transgene expression, but a beneficial effect on diaphragm force-generating capacity was observed in both groups of animals. We conclude the following: (1) short-term transduction of the diaphragm is more efficient in mdx than in normal mice; (2) AV leads to reduced force production by the diaphragm, with this effect being more pronounced in normal than in mdx in the early (but not the late) postinjection period; and (3) immunosuppressive therapy with cyclosporine has a partially protective effect on muscle function after AV administration, which is apparently unrelated to sparing of transduced fibers from elimination by the host immune system. These findings have important implications for the application of AV-mediated dystrophin gene transfer to the treatment of DMD.
Am J Respir Cell Mol Biol 1995 Nov
PMID:Efficiency and functional consequences of adenovirus-mediated in vivo gene transfer to normal and dystrophic (mdx) mouse diaphragm. 757 85


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