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

The severe Duchenne type of muscular dystrophy is inherited as an X-linked recessive trait. Approximately two thirds of healthy female heterozygous carriers have a high serum creatine kinase (SCK). A suspected carrier with a normal SCK level therefore, presents an important problem in genetic counselling. Based on Bayesian methods, Emery and Hollyway derived a formula which is applicable when the sporadic case is either the son or brother of a consultant and which also includes information on SCK levels in the consultant and in normal daughters and sisters. The present paper describes the results obtained with use of this formula in 27 families with at least a propositus with Duchenne muscular dystrophy.
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PMID:[Estimation of the probability of heterozygosity in Duchenne-type progressive muscular dystrophy]. 728 70

Clinical, electromyographic, and muscle biopsy findings in the two largest known families with Emery-Dreifuss humeroperoneal muscular dystrophy indicate that this is an X-linked recessive muscle disease with stereotyped clinical manifestations but with variable pathological and electromyographic characteristics. Elbow contractures, involvement of humeral muscles, hyporeflexia, and abnormal electrocardiograms are present in our patients. The disorder is associated with a potentially lethal cardiac arrhythmia that should be managed by pacemaker insertion. The skeletal muscle disease is slowly progressive and is usually not life threatening. Muscle biopsy commonly shows type I fiber atrophy. Electromyography usually indicates myopathy, though the classic findings of myopathy may not be present in every muscle.
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PMID:Emery-dreifuss humeroperoneal muscular dystrophy: an x-linked myopathy with unusual contractures and bradycardia. 729 29

In this report, we study the suitable conditions for myoblast cultures through analysis of myoblast growth and differentiation, and then try to develop a mouse model for myoblast transfer therapy (MTT). Recently, some research has indicated that Muscular Dystrophy Murine Mice (MDX) have an X-linked recessive dystrophin deficiency which is caused by dystrophin gene point mutation at the X chromosome. Therefore, MDX mice are usually used for MTT models of muscular dystrophy disease. Control mice, C57BL10/SCSN (B-10) were chosen as a source of normal myoblasts. Myoblasts isolated from the hindlimb muscle tissues of two- to three-day-old neonatal B-10 mice were cultured in vitro for one to seven days. Through our modifyied techniques of isolation and culturing conditions, a myoblast purity of 70% could be achieved, with fibroblast the only contaminating cell type. The proliferative capacity and the doubling time of myoblasts were counted from analysis of growth kinetics. While differentiative capacity was analyzed morphologically, we found the fusion of myoblasts was time-dependent. Immunostaining myoblasts of different stages with anti-dystrophin antibody showed that purified myoblasts with the capacity of fusion can express dystrophin and can be utilized as a donating source in MTT. In the MTT experiment, eight young MDX mice were injected with normal myoblasts at a concentration of 1 x 10(6) cells. All transplated mice received daily cyclosporine A injection for immunosuppression. Two to three months later, dystrophin was found in the myoblast-transferred muscles while staining immunocytochemically. The result suggests that we successfully transferred the normal dystrophin gene from the normal myoblasts into the MDX mice since their myoblast-injected muscle could express dystrophin.
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PMID:[Study of myoblast culture and myoblast transfer therapy in dystrophic mice]. 765 Jul 79

Duchenne (DMD) and Becker (BMD) muscular dystrophy are allelic X-linked recessive diseases caused by a mutation in the dystrophin gene located on the short arm of chromosome X (Xp21). The dystrophin gene is the largest gene known in humans, extending over 2300 kb and containing more than 70 exons coding for a 420 KD protein comprising 3685 amino acids. The gene is highly unstable, with a high percentage of deletions and rearrangements. A third of dystrophin mutations are new mutations. The frequency of DMD is 1:3500 liveborn males, and that of BMD 1:10000. These dystrophies are severe, progressive, and lethal. BMD/DMD patients and 2/3 of female carriers have high levels of creatine phosphokinase (CK). During the past 5 years, 169 families with patients affected by progressive muscular dystrophy were examined and counselled. We were able to exclude the diagnosis of DMD/BMD in 49 families on the basis of clinical symptoms and signs, normal dystrophin on biopsy (11 families) and/or the absence of linkage to chromosome X by analysis of RFLP derived haplotypes. Molecular analysis was performed on 111 DMD/BMD families (five BMD and 106 DMD) with 81 available probands. This study resulted in the establishment in Israel of an integrated diagnostic protocol for DMD/BMD, employing genetic, biochemical and molecular techniques. Molecular analysis provided most of the families with new and essential information.
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PMID:A molecular survey of Israeli Duchenne and Becker muscular dystrophy patients. 785 72

Duchenne and Becker muscular dystrophy (DMD and BMD) are X-linked recessive diseases caused by defective expression of dystrophin. The mdx mouse, an animal model for DMD, has a mutation that eliminates expression of the 427K muscle and brain isoforms of dystrophin. Although these animals do not display overt muscle weakness or impaired movement, the diaphragm muscle of the mdx mouse is severely affected and shows progressive myofibre degeneration and fibrosis which closely resembles the human disease. Here we explore the feasibility of gene therapy for DMD by examining the potential of a full-length dystrophin transgene to correct dystrophic symptoms in mdx mice. We find that expression of dystrophin in muscles of transgenic mdx mice eliminates the morphological and immunohistological symptoms of muscular dystrophy. In addition, overexpression of dystrophin prevents the development of the abnormal mechanical properties associated with dystrophic muscle without causing deleterious side effects. Our results provide functional evidence for the feasibility of gene therapy for DMD.
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PMID:Overexpression of dystrophin in transgenic mdx mice eliminates dystrophic symptoms without toxicity. 835 80

Adult male patients affected with Becker (BMD, N = 22), limb girdle (LGMD, N = 22) and facioscapulohumeral (FSHMD, N = 18) muscular dystrophy were interviewed to assess for the first time how the disease's severity and recurrence risk (RR) magnitude alter their social adjustment. BMD (X-linked recessive) is the severest form and confers an intermediate RR because all daughters will be carriers, LGMD (autosomal-recessive) is moderately severe with a low RR in the absence of consanguineous marriage, and FSHMD (autosomal-dominant) is clinically the mildest of these three forms of MD but with the highest RR, of 50%. Results of the semistructured questionnaire [WHO (1988): Psychiatric Disability Assessment Schedule] showed no significant difference between the three clinical groups, but more severely handicapped patients as well as patients belonging to lower socioeconomic levels from all clinical groups showed poorer social adjustment. Taken together, myopathic patients displayed intermediate social dysfunction compared to controls and schizophrenics studied by Jablensky [1988: WHO Psychiatric Disability Assessment Schedule]. Since the items of major dysfunction proportion among myopathic patients concern intimate relationships (70%), interest in working among those unemployed (67%), and social isolation (53%), emotional support and social and legal assistance should concentrate on these aspects. Interestingly, the results of this study also suggest that high RRs do not affect relationships to the opposite sex.
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PMID:Social adjustment in adult males affected with progressive muscular dystrophy. 951 80

Duchenne's muscular dystrophy (DMD) is an X-linked recessive disease. Clinical descriptions of the disorder focus principally on skeletal muscle degeneration. Another manifestation, which involves the gastrointestinal tract, may be fatal. But its prevalence remains undefined. We report here a case of acute gastroparesis associated with Duchenne's muscular dystrophy. In our case, the patient's symptoms were improved by prokinetic agents and timely decompression in life-threatening acute gastric dilatation.
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PMID:Acute gastroparesis in Duchenne's muscular dystrophy. 958 59

Duchenne muscular dystrophy (DMD), with an incidence of one in 3500 male new borns, and its milder variant, Becker muscular dystrophy (BMD), are allelic X-linked recessive disorders, caused by mutations in the gene coding for dystrophin, a 427 kD cytoskeleton protein. There are no available molecular markers to differentiate these two. The purpose of this study was to study genetic polymorphism in muscular dystrophy and explore its potential in discriminating these two allelic forms of the disease. The results revealed unambiguously the presence of three transcripts : 598bp, 849bp and 1583bp long which are selectively expressed in the muscles afflicted with muscular dystrophy as compared to the normal muscle. 1583bp gene transcript was conspicuously present in the muscle tissues of both DMD and BMD patients whereas 598bp and 849bp long transcripts were exclusively present in DMD but not in BMD patients or normal human subjects. These gene transcripts had no sequence homology with dystrophin gene and these were also present in the families belonging to DMD and BMD patients. These results point to the fact that based upon the selective expression of these three gene transcripts, one could not only differentiate between DMD and BMD diseases at the molecular level, but also between normal and dystrophic muscle. Further, these findings also reveal that apart from dystrophin gene, these gene transcripts may also be responsible for the differential progression of DMD/BMD phenotype.
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PMID:Genetic polymorphism in muscle biopsies of Duchenne and Becker muscular dystrophy patients. 1051 83

The mdx mouse, an animal model of Duchenne muscular dystrophy, develops an X-linked recessive inflammatory myopathy. During onset of disease and height of myonecrosis, mdx mice also display important changes in the microenvironment of lymphoid tissues. Draining lymph nodes showed reduced cellularity and atrophy accompanied by intense immunolabeling for fibronectin, laminin, and type-IV collagen. Following clinical amelioration of dystrophy, mdx mice showed enhanced cellularity and a consistent increase in the absolute numbers of CD4(+) and CD8(+) cells expressing alpha4(high) and alpha5(high) extracellular matrix receptors. Furthermore, infiltrating cells in the proximity of myonecrosis expressed alpha4, alpha5, and alpha6 integrin chains during both height of myonecrosis and muscular tissue regeneration. Such results indicate that during distinct phases of muscular dystrophy, altered expression of extracellular matrix ligands and receptors may be influencing myonecrosis by promoting adhesion and migration of mononuclear cells into the altered skeletal muscle and toward local draining lymphoid tissue.
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PMID:Expression of extracellular matrix ligands and receptors in the muscular tissue and draining lymph nodes of mdx dystrophic mice. 1052 90

Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked recessive or autosomal dominant progressive muscular dystrophy characterized by progressive muscle wasting and weakness with scapulo-humero-peroneal distribution, early contracture and cardiomyopathy with conduction block. The responsible gene for EDMD, designated as 'STA', has been mapped to Xq 28 and cloned. It encodes a serine-rich protein of 254-amino-acid, called 'emerin', localized in the inner nuclear rim. We performed genetic analysis of a 23-year-old male clinically diagnosed as EDMD and found a novel point mutation. Total RNA was extracted from skeletal muscle and reverse-transcription and polymerase chain reaction amplification was performed using a set of oligonucleotide primers between 5'-flanking site of exon 1 and exon 4. Our patient gave a smaller PCR product (about 30 bp) than normal control. The determined cDNA sequence revealed a deletion of 29 bp, spanning position 164 to 192 in exon 1. To clarify the mutant allele, we performed genomic DNA sequence. Genomic DNA sequence from the initiation of exon 1 to the upstream lesion of exon 2 confirmed a novel point mutation G to C, at nucleotide 197 in the donor splice site of intron 1. This point mutation may interfere with the correct splicing of the mRNA and cause frameshift, resulted in truncation of predicted protein by premature stop. We report a novel point mutation G to C, at nucleotide 197 in the intron 1 of STA gene corresponding the truncation of predicted protein, which differs from any of the previously reported mutations.
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PMID:[A novel splice-site mutation in the STA gene in a Japanese patient with Emery-Dreifuss muscular dystrophy]. 1068 37


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