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

We review recent publications involving molecular biology and heart failure. There was some further evolution in our knowledge of the basis for the simplest of molecular genetic diseases--single gene disorders. This year, hypertrophic cardiomyopathy had further genes identified as causative mutations; was shown to have the same genetic defects in spontaneous and familial cases; and demonstrated phenotypic alteration by environmental factors. Several rare cardiomyopathies were linked to the dystrophin gene, previously identified as the mutated gene responsible for forms of muscular dystrophy. Molecular methods were applied to linking viral infection to dilated cardiomyopathy by hunting for viral genomes in heart muscle, and for seeking mutations in mitochondrial DNA. Molecular treatment of restenosis after angioplasty showed promise through the application of gene transfer to vascular tissue by oligonucleotides as well as adenovirus-mediated gene transfer. The ethical aspects of diagnosing and treating human disease using genetic information, which receive frequent discussion in print, are also reviewed.
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PMID:The molecular and cellular biology of heart failure. 804 84

We report on multicolor fluorescence in situ hybridization protocols for the simultaneous visualization of deletion-prone regions for carrier detection of Duchenne/Becker (DMD/BMD) muscular dystrophy. Cosmid and yeast artificial chromosome (YAC) clones specific for preferentially deleted subregions of the dystrophin gene were labeled differentially and detected with three different fluorochromes using digital imaging microscopy. This approach allows for an assessment of the carrier status of female relatives even in families where no index patient is available. Cosmid and YAC clones, and different probe-generation protocols are compared with respect to their feasibility for carrier detection. The use of histone-depleted interphase nuclei (Halo-preparations) for deletion mapping is demonstrated and shown to have a resolution power of 5 kb.
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PMID:Multicolor fluorescence in situ hybridization on metaphase chromosomes and interphase Halo-preparations using cosmid and YAC clones for the simultaneous high resolution mapping of deletions in the dystrophin gene. 812 73

Methods of molecular genetics (Southern's hybridization and DNA amplification by the PCR method) were used to search the DNA of patients suffering from the Duchenne (DMD) and the Becker (BMD) type of progressive muscular dystrophy for deletions in the dystrophin gene. The series consisted of 29 patients with DMD and 2 patients with BMD. As hybridization probes cloned cDNA sections were used designated as CF56a, CF56b, 1-2a, 2b-3, 4-5a, 5b-7 and 8. With the PCR methods means for exons 8, 19, 45 and 48 were used. No deletion was found in either of the BMD patients. In 13 (44.8%) of the 29 DMD patients deletion with at least one cDNA probe was found. Most deletions were detected with the probes 8 (46.2%) and 1-2a (30.8%). The high proportion of deletions in the etiology of DMD/BMD has both a high differential diagnostic value and allows to make direct prenatal diagnosis as well as to determine transmission in these families with subsequent elimination of the risk of diagnostic error resulting from recombination in DNA diagnosis by means of binding. (Tab. 1, Fig. 2, Ref. 20.)
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PMID:[Molecular genetic analysis of deletions in the Duchenne and Becker types of progressive muscular dystrophy]. 817 87

Clinical differential diagnosis between Becker muscular dystrophy (BMD) and limb gridle muscular dystrophy (LGMD) may be difficult because the BMD clinical phenotype tends to overlap with other limb girdle syndromes, especially with LGMD. Therefore we studied the expression of dystrophin, the protein product of the Becker and Duchenne muscular dystrophy gene, in muscle biopsy specimens of 30 patients (18 males, of whom 15 represented spradic cases, and 12 females) diagnosed as having LGMD according to traditional clinical, electrophysiological and histological criteria. For dystrophin analysis, six different monoclonal antibodies directed against different epitopes of the dystrophin molecule were used. Immunocytochemically, five of the 30 LGMD patients (17%) showed abnormal dystrophin staining patterns diagnostic of BMD. Western blotting in these five patients, all sporadic cases, showed dystrophin of reduced size and/or abundance. Analysis of blood or muscle DNA using multiplex polymerase chain reaction revealed deletions in the dystrophin gene in three of the five. Thus, 5 of 15 (33%) sporadic male patients previously thought to have LGMD were identified as having BMD.
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PMID:Abnormal dystrophin expression in patients with limb girdle syndromes. 819 19

Duchene muscular dystrophy (DMD) is a fatal progressive X-linked muscle disorder, caused by mutations in the dystrophin gene. We have investigated adenovirus-mediated transfer of a dystrophin minigene in a mutant mouse lacking dystrophin, the mdx mouse. We report here that six months after a single intramuscular injection of a recombinant adenovirus containing a human dystrophin minigene, a large number of dystrophin-positive fibres are still detected in the injected muscles. Moreover, although the minigene encodes a truncated protein, its expression is able to protect the fibres efficiently against the degeneration process that affects the dystrophin-deficient mdx myofibres.
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PMID:Long-term correction of mouse dystrophic degeneration by adenovirus-mediated transfer of a minidystrophin gene. 825 38

Idiopathic dilated cardiomyopathy (DCM) is characterised by ventricular dilatation and impaired systolic function resulting in congestive heart failure and frequently death. A dilated cardiomyopathy is common in patients with symptomatic Duchenne/Becker muscular dystrophy, a disease caused by dystrophin gene defects. However, cardiomyopathy is rarely the predominant clinical feature of this form of muscular dystrophy. To determine whether dystrophin gene defects might account for a significant number of patients with apparently isolated idiopathic DCM, we performed dystrophin gene analysis in 27 DCM patients, who were ascertained as part of a prospective study on idiopathic DCM. No dystrophin gene defects were found in our patients, whose average age was 50 years. These data suggest that dystrophin defects are not a common cause of idiopathic DCM in this age group in the absence of skeletal muscle cramps or weakness.
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PMID:Dystrophin analysis in idiopathic dilated cardiomyopathy. 830 53

The first three exons of the human muscle dystrophin gene were expressed as a beta-galactosidase fusion protein. This protein was then used to prepare two monoclonal antibodies (mAbs) which react with native dystrophin on frozen muscle sections and with denatured dystrophin on western blots but which do not cross-react with the dystrophin-related protein, utrophin. Both mAbs recognized dystrophin in muscular dystrophy (MD) patients with deletions of exon 3, and further mapping with 11 overlapping synthetic peptides showed that they both recognize an epitope encoded by the muscle-specific exon 1. Neither mAb recognizes the brain dystrophin isoform, confirming the prediction from mRNA data that this has a different N-terminus. One Becker MD patient with a frameshift deletion of exons 3-7 is shown to produce dystrophin which reacts with the N-terminal mAbs, as well as with mAbs which bind on the C-terminal side of the deletion. The data suggest that transcription begins at the normal muscle dystrophin promoter and that the normal reading frame is restored after the deletion. A number of mechanisms have been proposed for restoration of the reading frame after deletion of exons 3-7, but those which predict dystrophin with an abnormal N-terminus do not appear to be major mechanisms in this patient.
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PMID:Monoclonal antibodies against the muscle-specific N-terminus of dystrophin: characterization of dystrophin in a muscular dystrophy patient with a frameshift deletion of exons 3-7. 831 78

A single base change in the 5' splice-site of intron 19 has been identified as the cause of the Becker muscular dystrophy in a family which had previously been deduced to carry both a major deletion and another, at that stage unidentified, mutation in the same dystrophin gene [Laing et al., 1992]. RNA from a muscle biopsy of one of the Becker muscular dystrophy patients in the family was analysed using the reverse transcriptase-polymerase chain reaction (RT-PCR) to study the mature gene transcript. Exon 19 was deleted from the dystrophin mRNA but present at the genomic level. The loss of exon 19 in the mature mRNA was found to be associated with an A to C mutation in the 5' splice site of intron 19. Deletion of exon 19 should alter the reading frame of the mRNA and be associated with a severe form of muscular dystrophy; however, low levels of normal-size dystrophin message and dystrophin were present in this patient. The distance between the splice-site mutation and the secondary deletion in the dystrophin gene is such that it would seem unlikely that the initial base change could act as a premutation for the deletion. Specific primers to detect the splice-site mutation have been designed and used to genotype all relatives.
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PMID:Two distinct mutations in a single dystrophin gene: identification of an altered splice-site as the primary Becker muscular dystrophy mutation. 832 22

The molecular defect in Duchenne muscular dystrophy is well established as being due to mutations at Xp21 which disrupt the normal synthesis of the 14kb dystrophin mRNA. More recently, several groups have identified a 4.8kb transcript from this locus which shares exons with the carboxy-terminal region of the dystrophin gene. In this paper we present evidence for an additional 2.2kb mRNA transcript. The 5' untranslated region and first 7 amino acids are identical to that published for the 4.8kb transcript. The position of the translational stop codon and 3' untranslated region is similar to that previously described as the truncated fetal dystrophin isoform. This 2.2kb mRNA has a similar tissue distribution to that described for the 4.8kb mRNA but unlike the other transcripts from the DMD locus, the 2.2kb mRNA is expressed in early development. The relevance of this transcript in the clinical expression of muscular dystrophy and developmental delay is discussed.
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PMID:Apo-dystrophin-3: a 2.2kb transcript from the DMD locus encoding the dystrophin glycoprotein binding site. 851 89

Two sisters with muscular dystrophy of Becker-like clinical features presented. Muscle weakness was most prominent in the pelvic girdle, but in the elder sister the distal muscles of the lower extremities were also affected. The progression was different in the siblings: The older sister showed a more pronounced deterioration than the younger. The family history was negative in four generations including their brother and youngest sister. Serum creatinine kinase activities increased considerably. Electromyogram and muscle biopsy specimens revealed myopathic changes characteristic of muscular dystrophy. Chromosomal analysis confirmed normal 46,XX karyotype. DNA analysis with all cDNA probes spanning the entire dystrophin gene failed to reveal any intragenic deletion or duplication on southern blot. Immunohistochemistry for dystrophin using monoclonal antibodies against the rod and C-terminal domains showed normal continuous staining at the sarcolemma of the muscle fibers in the biopsy specimens of both patients. The results practically exclude the possibility of Xp21 myopathy, and it seems reasonable to classify these patients as having autosomal recessive childhood muscular dystrophy.
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PMID:Becker-like muscular dystrophy in sisters. 852 70


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