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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Subtraction hybridization techniques were used to isolate 91 cDNA clones which are overexpressed in normal control skeletal muscle relative to muscle from patients with myotonic muscular dystrophy. The gene responsible for myotonic dystrophy (DM) has been localized to the 19q13.2-13.3 region of chromosome 19. To test as a candidate gene for DM, clones which represent differences in transcription are analyzed for localization to chromosome 19. One clone, designated MSL 366, was found to be on the long arm of chromosome 19 distal to the CKMM gene at 19q13.2. Sequence analysis confirmed that MSL 366 is the cDNA for human slow skeletal muscle troponin T. A genomic clone has been isolated and linkage studies with DM are in progress.
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PMID:Isolation and localization of a slow troponin (TnT) gene on chromosome 19 by subtraction hybridization of a cDNA muscle library using myotonic dystrophy muscle cDNA. 170 83

A 6-yr-old boy who presented with brown urine due to myoglobinuria and who was otherwise virtually asymptomatic was diagnosed as having Becker muscular dystrophy on the basis of a greatly elevated creatine kinase, muscle biopsy, dystrophin analysis, and a deletion of exons 3-7 in the dystrophin gene. Fifteen months later, during a general anaesthetic for dental treatment, he had a cardiac arrest associated with acute rhabdomyolysis, hyperkalaemia and hypocalcaemia. He died 4 days later. This case is reported to highlight this rare but potentially fatal complication of anaesthesia in muscular dystrophy, and to discuss possible ways of preventing such a catastrophe.
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PMID:Fatal rhabdomyolysis complicating general anaesthesia in a child with Becker muscular dystrophy. 182 95

Dystrophia myotonica (Steinert's disease) is the most common hereditary disease of the neuromuscular system in adults. Its mode of inheritance is autosomal dominant. The gene responsible for its is located on chromosome 19 in the linkage domain of the loci for the apolipoproteins C2, C1 und E and of the creatine kinase of skeletal muscle (CKMM). Myotonic dystrophy is categorized in an adult and in a congenital form. In the adult form, the characteristic findings are muscular atrophy in certain regions of the body (face, neck and distally in the extremities) and myotonia. Cataract, intraocular hypotension, gonadal atrophy, conduction abnormalities in the heart and hearing deficiencies appear quite often in the course of the disease. In the congenital form, general muscle weekness (particularly pronounced in the face) is the leading finding, combined with retarded loco motor and mental development. A decisive criterion for the diagnosis of this form is the occurrence of myotonic dystrophy in the patient's mother. Electromyographic investigation is indicated when a suspicion of myotonic dystrophy cannot be ascertained on the basis of clinical and genetic findings. Myotonic runs in the EMG will then corroborate the suspicion. Recent electrophysiological investigations have indicated that at least three different types of channels for the passage of ions through the membrane of the skeletal muscle cells show abnormal behaviour, i.e. the channel for Cl-, Na+ and K+. These findings corroborate the hypothesis that the abnormality responsible for myotonic dystrophy is situated in the membrane systems. A pharmacological treatment of the muscular dystrophy has not yet been developed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Dystrophia myotonica (Steinert disease)--a frequently misdiagnosed disease]. 219 75

We report on the physical ordering of genes in a relatively small area of chromosome 19, segment q13, containing the locus for myotonic dystrophy (DM), the most frequent heritable muscular dystrophy of adulthood in man. DNAs from somatic cell hybrids with der 19q products that carry a breakpoint across the muscle-specific creatine kinase (CKMM) gene were analyzed by Southern blotting using probes for CKMM, APOC2, and the repair genes ERCC1 and ERCC2. Results were combined with data from CHEF and field inversion-gel-electrophoresis separation of large-sized DNA restriction fragments to establish a map localizing both DNA-repair genes and the CKMM gene within the same 250 kb of DNA, the order being cen-CKMM-ERCC2-ERCC1-ter, with APOC2 being at more than 260 kb proximal to CKMM. Transcriptional start sites of the CKMM and DNA-repair genes are all on the telomeric side of the genes. Our results provide a framework for the construction of a larger physical map of the area, which will facilitate the search for the DM gene.
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PMID:A long-range restriction map of the human chromosome 19q13 region: close physical linkage between CKMM and the ERCC1 and ERCC2 genes. 230 1

The human chromosomal assignments of genes of the creatine kinase (CK) family--loci for brain (CKBB), muscle (CKMM), and mitochondrial (CKMT) forms--were studied by Southern filter hybridization analysis of DNAs isolated from a human x rodent somatic cell hybrid clone panel. Probes for the 3'-noncoding sequences of human CKBB and CKMM hybridized concordantly only to DNAs from somatic cell hybrids containing chromosomes 14 and 19, respectively. Thus the earlier assignment of the gene coding for the CKBB isozyme to chromosome 14 was confirmed by molecular means, as was the provisional assignment of CKMM to the long arm of chromosome 19. A probe containing canine sequences for CKMM cross-hybridized with human sequences on chromosomes 14 and 19, a result consistent with the assignments of CKBB and CKMM. A probe containing human sequences for CKMT enabled the provisional assignment of CKMT to human chromosome 15. Independent hybrids with portions of the long arm of chromosome 19 missing indicated the order of genes on the long arm of chromosome 19 as being cen-GPI-(TGFB, CYP1)-[CKMM, (APOC2-ERCC1)]-(CGB, FTL). The unexpectedly more distal location of APOC2 among the genes on the long arm--and APOC2's close association with CKMM--is discussed with respect to the close linkage relationship of APOC2 to myotonic muscular dystrophy.
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PMID:Human creatine kinase genes on chromosomes 15 and 19, and proximity of the gene for the muscle form to the genes for apolipoprotein C2 and excision repair. 340 Jun 41

The natural variability of plasma creatine kinase activity has been examined in patients suffering from muscular dystrophy and in normal subjects. The coefficient of variation of the plasma creatine kinase activities was found to be large (approximately 35%) in both patients with Duchenne muscular dystrophy and normal control subjects. A comparison of the plasma activities of creatine kinase with other muscle-derived enzymes suggests that the cause of this variability is changes in the release of enzymes from muscle. Data obtained concerning the effect of physical activity on plasma creatine kinase activity are contradictory, but several young patients with Duchenne muscular dystrophy and a very high creatine kinase activity (greater than 5000 IU/liter) showed a decreased activity following admission to hospital. An estimate of the rate of efflux of certain kinase from muscle has been made, indicating that young ambulant patients with Duchenne muscular dystrophy have a grossly elevated muscle creatine kinase efflux (495.0 +/- 61.3 IU/kg muscle/hr) compared to control subjects (1.4 +/- 0.5 IU/kg muscle/hr).
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PMID:An examination of some factors influencing creatine kinase in the blood of patients with muscular dystrophy. 356 34

An X chromosome-linked mouse mutant (gene symbol, mdx) has been found that has elevated plasma levels of muscle creatine kinase and pyruvate kinase and exhibits histological lesions characteristic of muscular dystrophy. The mutants show mild clinical symptoms and are viable and fertile. Linkage analysis with four X chromosome loci indicates that mdx maps in the Hq Bpa region of the mouse X chromosome. This gives a gene order of mdx-Tfm-Pgk-1-Ags, the same as for the equivalent genes on the human X chromosome.
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PMID:X chromosome-linked muscular dystrophy (mdx) in the mouse. 658 3

Myotonic dystrophy (DM) is an autosomal dominant, multisystem disorder and the most common adult form of muscular dystrophy. The age of onset and degree of severity of DM is highly variable. The biochemical defect in DM is unknown. DM was the first autosomal disorder to be localised by genetic linkage to protein markers (Lu, Se, C3), and assigned to chromosome 19. Linkage studies in DM families using RFLPs as polymorphic markers refined the mapping position to 19q13.1-13.2 distal to the BCL3, apoCII, CKM and ERCCI genes. Based on the linkage data, healthy individuals from DM families request a pre-symptomatic test. The information is of use in planning their family, if at high risk they can choose to have prenatal diagnosis. We have studied ten unrelated DM families by linkage analysis. The DNA probes to detect the various RFLPS were either from the vicinity of BCL3, ApoCII, CKMM and ECCRI genes or anonymous DNA probes. Linkage analysis in the DM families enabled us to determine the carrier status of healthy individuals and to perform prenatal diagnosis at a confidence of > 99%. In two families the DM diagnosis was in doubt and we did not include them in the combined analysis. Linkage disequilibrium was noted with two RFLPs pDIO/Pst1 and p37.1/BamH1. Both DNA probes were isolated by Shaw and his group in Cardiff. In six out of eight families, the DM chromosome was associated with allele 3 of pDIO/Pst1 and allele 1 of p37.1/BamH1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myotonic dystrophy: molecular analysis of Israeli patients. 785 74

In humans, a subset of cases of Limb-girdle muscular dystrophy (LGMD) arise from mutations in the genes encoding one of the sarcoglycan (alpha, beta, gamma, or delta) subunits of the dystrophin-glycoprotein complex. While adeno-associated virus (AAV) is a potential gene therapy vector for these dystrophies, it is unclear if AAV can be used if a diseased muscle is undergoing rapid degeneration and necrosis. The skeletal muscles of mice lacking gamma-sarcoglycan (gsg-/- mice) differ from the animal models that have been evaluated to date in that the severity of the skeletal muscle pathology is much greater and more representative of that of humans with muscular dystrophy. Following direct muscle injection of a recombinant AAV [in which human gamma-sarcoglycan expression is driven by a truncated muscle creatine kinase (MCK) promoter/enhancer], we observed significant numbers of muscle fibers expressing gamma-sarcoglycan and an overall improvement of the histologic pattern of dystrophy. However, these results could be achieved only if injections into the muscle were prior to the development of significant fibrosis in the muscle. The results presented in this report show promise for AAV gene therapy for LGMD, but underscore the need for intervention early in the time course of the disease process.
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PMID:Rescue of skeletal muscles of gamma-sarcoglycan-deficient mice with adeno-associated virus-mediated gene transfer. 1093 22

Recombinant adeno-associated virus (rAAV) vectors allow efficient gene transfer and expression in the muscle; therefore, rAAVs represent a potential gene therapy vector for muscular dystrophies. For further investigations, we used a mouse muscular dystrophy model (gsg(-/-) mice) gamma-sarcoglycan, a subunit of the dystrophin-glycoprotein complex, is missing. gsg(-/-) mice develop progressive dystrophy representative of a severe human phenotype disease. We previously showed high levels and stable expression of gamma-sarcoglycan in myofibers after direct muscle injection into gsg(-/-) mice of a recombinant AAV vector (AAV.dMCK.gSG) carrying the gamma-sarcoglycan cDNA driven by a muscle-specific promoter (truncated version of muscle creatine kinase). Here, we show that when gamma-sarcoglycan expression is driven by the ubiquitous cytomegalovirus (CMV) promoter (AAV.CMV.gSG), lower levels of transgene expression are observed and are associated with a humoral response to gamma-sarcoglycan. When using an rAAV vector, expressing the highly immunogenic product gamma-galactosidase under the CMV promoter (AAV.CMV.LacZ), we measured a strong cellular and humoral immune response to the transgene after intramuscular injection into gsg(-/-) mice. This study suggests that restriction of transgene expression to the muscle is an important criterion for the treatment of muscular dystrophies and will aid in the design of protocols for gene therapy.
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PMID:Muscle-specific promoters may be necessary for adeno-associated virus-mediated gene transfer in the treatment of muscular dystrophies. 1117 57


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