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

The gene for Duchenne (DMD) and Becker (BMD) types of muscular dystrophy has been isolated by Kunkel's and Worton's groups and shown to be the largest one over known in human, spanning more than 65 exons distributed over 2,500 kb in P21 region of X-chromosome. Fourteen kb cDNA encodes 427 kD cytoskeletal protein "dystrophin", supposed to form an anti-parallel homodimer like alpha-actinin and spectrin. The polyclonal antibodies against the synthetic peptides or fusion proteins predicted from dystrophin cDNA disclosed the complete absence of dystrophin at the surface membrane of both skeletal and cardiac muscles of DMD in marked contrast with the continuous and uniform staining in normal muscles. In manifested carriers, the mosaic expression of dystrophin was observed at the surface membrane of the skeletal muscle. BMD, which is thought to be allelic to DMD, revealed a faint or patchy immunostaining along with the abnormal and/or lower amount of dystrophin. In BMD, there is an intimate connection between the amount of dystrophin and the severity of the clinical course. It should be noted that 5 out of 39 patients with clinical diagnosis of limb-girdle (L-G) muscular dystrophy showed a patchy staining pattern, suggesting BMD not L-G. On the basis of dystrophin discovery, a possible therapeutic trial of DMD is discussed.
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PMID:[Molecular pathology of Duchenne and Becker muscular dystrophy]. 209 74

X-chromosome-specific DNA probes were used to study a new type of muscular dystrophy (MD) presented by two boys in a family in which there was no previous history neuromuscular disease. Clinical investigations showed evidence of myogenic myopathyia, but its exact nature could not be established. The results of the DNA analysis exclude DMD, BMD and EMD. We suggest a probable autosomal recessive inheritance for the MD seen in this family.
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PMID:A new type of muscular dystrophy in two brothers: analysis by use of DNA probes suggests autosomal recessive inheritance. 322 98

Recent progress has resulted in part of the gene mutated in Duchenne and the milder Becker muscular dystrophies being cloned and has suggested that the gene itself extends over 1,000 to 2,000 kilobases (kb). To study how mutations in this gene affect muscle development and integrity, it would be of interest to have available a mouse model of the human disease. The mouse mdx mutation affects muscle and confers a mild dystrophic syndrome, but it is not clear whether this mutation is equivalent to Duchenne/Becker muscular dystrophy in man. Here we describe the use of two sequences from the human Duchenne muscular dystrophy (DMD) gene that cross-hybridize to mouse X-linked sequences to localize the gene homologous to DMD in the mouse. Both sequences map to the region of 10 centimorgan lying between the Tabby (Ta) and St14-1 (DxPas8) loci, close to the phosphorylase b kinase locus (Phk). By analogy with the human X-chromosome, we conclude that the region in the mouse around the G6pd and St14-1 loci may contain two genes corresponding to distinct human myopathies: Emery Dreifuss muscular dystrophy which is known to be closely linked to St14-1 in man and the DMD homologue described here.
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PMID:Localization of the region homologous to the Duchenne muscular dystrophy locus on the mouse X chromosome. 360 Jul 94

The most common muscular dystrophy, Duchenne muscular dystrophy (DMD), is an X-linked disorder that ordinarily has full clinical expression only in males. Reports of typical clinical features in females are rare but have occurred with a phenotypically identical autosomal recessive muscular dystrophy as well as in females with X-chromosome abnormalities such as the Turner syndrome. A girl with full expression of DMD due to a 46 XY karyotype is reported, and other clinical conditions in which expression of the DMD gene occurs in females are reviewed.
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PMID:Duchenne muscular dystrophy in a 46 XY female. 369 49

A 3 1/2-year-old child with progressive muscular dystrophy (PMD) and congenital adrenal hypoplasia (CAH) is described. Symptoms and signs of adrenocortical insufficiency appeared shortly after birth. Despite corticosteroid therapy, the muscular weakness and elevated CK level continued. A diagnosis of Duchenne muscular dystrophy was made on the basis of clinical signs and characteristic muscle biopsy. The affection of his older brother suggests an X-linked recessive inheritance. The autopsy revealed a very rare combination of cytomegalic type CAH and PMD. This combination suggests that a small deletion of X-chromosome might be responsible for the two disorders.
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PMID:Progressive muscular dystrophy with congenital adrenal hypoplasia: an unusual autopsy case. 376 5

Preimplantation genetic diagnosis was performed in 122 embryos obtained by IVF from 11 patients carriers of haemophilia, Duchenne's muscular dystrophy, Barth's syndrome, cystic fibrosis, Pelizaeus-Merzbacher syndrome or Rett's syndrome. After multiplex polymerase chain reaction (PCR) or fluorescence in situ hybridization (FISH) analysis with multiple probes, 28 embryos diagnosed as not affected were replaced. Of these, eight implanted (28%) and produced three ongoing pregnancies, three deliveries of four babies and a biochemical pregnancy. However, one case screened for cystic fibrosis was misdiagnosed and the pregnancy was terminated. In order to evaluate the efficiency of multiplex PCR, 55 non-replaced embryos were reassessed by PCR or by FISH. Identical results were obtained in all cases. However, one embryo which had only X-chromosome specific amplification by PCR was found to be XO in all its cells by FISH. Although multiplex PCR is demonstrated to be reliable for sexing of human embryos, FISH has the additional advantages of supplying ploidy assessment while not being affected by contamination.
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PMID:Healthy deliveries from biopsied human embryos. 792 42

We review the extensive research conducted on the mdx mouse since 1987, when demonstration of the absence of dystrophin in mdx muscle led to X-chromosome-linked muscular dystrophy (mdx) being considered as a homolog of Duchenne muscular dystrophy. Certain results are contradictory. We consider most aspects of mdx skeletal muscle: (i) the distribution and roles of dystrophin, utrophin, and associated proteins; (ii) morphological characteristics of the skeletal muscle and hypotheses put forward to explain the regeneration characteristic of the mdx mouse; (iii) special features of the diaphragm; (iv) changes in basic fibroblast growth factor, ion flux, innervation, cytoskeleton, adhesive proteins, mastocytes, and metabolism; and (v) different lines of therapeutic research.
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PMID:Characteristics of skeletal muscle in mdx mutant mice. 1034 93

A man was identified with two X-chromosomal neuromuscular disorders, X-linked Charcot-Marie-Tooth disease (CMTX) and Becker muscular dystrophy (BMD). The neuropathy could be tracked in the family and was found to be caused by a mutation in the connexin32 gene on Xq13. 1. The muscular dystrophy was sporadic owing to a de novo deletion in the dystrophin gene located in band Xp21.2. Although these genetic alterations of the same X-chromosome are considered as physically independent, their combination resulted in a unique phenotype with severe wasting of proximal as well as distal muscles and rapid progression of both conditions.
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PMID:Becker muscular dystrophy combined with X-linked Charcot-Marie-Tooth neuropathy. 1079 9

The myogenic potential of bone marrow and fetal liver cells was examined using donor cells from green fluorescent protein (GFP)-gene transgenic mice transferred into chimeric mice. Lethally irradiated X-chromosome-linked muscular dystrophy (mdx) mice receiving bone marrow cells from the transgenic mice exhibited significant numbers of fluorescence(+) and dystrophin(+) muscle fibres. In order to compare the generating capacity of fetal liver cells with bone marrow cells in neonatal chimeras, these two cell types from the transgenic mice were injected into busulfantreated normal or mdx neonatal mice, and muscular generation in the chimeras was examined. Cardiotoxin-induced (or -uninduced, for mdx recipients) muscle regeneration in chimeras also produced fluorescence(+) muscle fibres. The muscle reconstitution efficiency of the bone marrow cells was almost equal to that of fetal liver cells. However, the myogenic cell frequency was higher in fetal livers than in bone marrow. Among the neonatal chimeras of normal recipients, several fibres expressed the fluorescence in the cardiotoxin-untreated muscle. Moreover, fluorescence(+) mononuclear cells were observed beneath the basal lamina of the cardiotoxin-untreated muscle of chimeras, a position where satellite cells are localizing. It was also found that mononuclear fluorescence(+) and desmin(+) cells were observed in the explantation cultures of untreated muscles of neonatal chimeras. The fluorescence(+) muscle fibres were generated in the second recipient mice receiving muscle single cells from the cardiotoxin-untreated neonatal chimeras. The results suggest that both bone marrow and fetal liver cells may have the potential to differentiate into muscle satellite cells and participate in muscle regeneration after muscle damage as well as in physiological muscle generation.
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PMID:Muscle regeneration by reconstitution with bone marrow or fetal liver cells from green fluorescent protein-gene transgenic mice. 1188 27

Although the primary abnormality in dystrophin is the underlying cause for mdx (X-chromosome-linked muscular dystrophy), abnormal Ca2+ handling after sarcolemmal microrupturing appears to be the pathophysiological mechanism leading to muscle weakness. To develop novel pharmacological strategies for eliminating Ca2+-dependent proteolysis, it is crucial to determine the fate of Ca2+-handling proteins in dystrophin-deficient fibres. In the present study, we show that a key luminal Ca2+-binding protein SAR (sarcalumenin) is affected in mdx skeletal-muscle fibres. One- and two-dimensional immunoblot analyses revealed the relative expression of the 160 kDa SR (sarcoplasmic reticulum) protein to be approx. 70% lower in mdx fibres when compared with normal skeletal muscles. This drastic reduction in SAR was confirmed by immunofluorescence microscopy. Patchy internal labelling of SAR in dystrophic fibres suggests an abnormal formation of SAR domains. Differential co-immunoprecipitation experiments and chemical cross-linking demonstrated a tight linkage between SAR and the SERCA1 (sarcoplasmic/endoplasmic-reticulum Ca2+-ATPase 1) isoform of the SR Ca2+-ATPase. However, the relative expression of the fast Ca2+ pump was not decreased in dystrophic membrane preparations. This implies that the reduction in SAR and calsequestrin-like proteins plays a central role in the previously reported impairment of Ca2+ buffering in the dystrophic SR [Culligan, Banville, Dowling and Ohlendieck (2002) J. Appl. Physiol. 92, 435-445]. Impaired Ca2+ shuttling between the Ca2+-uptake SERCA units and calsequestrin clusters via SAR, as well as an overall decreased luminal ion-binding capacity, might indirectly amplify the Ca2+-leak-channel-induced increase in cytosolic Ca2+ levels. This confirms the idea that abnormal Ca2+ cycling is involved in Ca2+-induced myonecrosis. Hence, manipulating disturbed Ca2+ handling might represent new modes of abolishing proteolytic degradation in muscular dystrophy.
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PMID:Drastic reduction of sarcalumenin in Dp427 (dystrophin of 427 kDa)-deficient fibres indicates that abnormal calcium handling plays a key role in muscular dystrophy. 1467 11


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