Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 25 year old woman, without family history of muscular dystrophy, had had an isolated lower limb hypertrophy since infancy and later experienced exercise-induced myalgia. Genomic DNA analysis showed a deletion of exons 45 to 52 of the dystrophin gene. Uncommon phenotypes of dystrophinopathies and consequences in genetic counselling in women are emphasised.
 ...
PMID:Sporadic lower limb hypertrophy and exercise induced myalgia in a woman with dystrophin gene deletion. 853 Sep 47

The mdx mouse has a mutated dystrophin gene and is used as a model for the study of Duchenne muscular dystrophy (DMD). We investigated whether regenerating mdx skeletal muscle contains the extracellular matrix protein tenascin-C (TN-C), which is expressed in wound healing and nerve regeneration. Prior to the initiation of muscle degeneration, both normal and mdx mice displayed similar weak staining for TN-C in skeletal muscle, but by 3 weeks of age the mice differed substantially. TN-C was undetectable in normal muscle except at the myotendinous junction, while in dystrophic muscle, TN-C was prominent in degenerating/regenerating areas, but absent from undegenerated muscle. With increasing age, TN-C staining declined around stable regenerated mdx myofibers. TN-C was also observed in muscle from dogs with muscular dystrophy and in human boys with DMD. Therefore, in dystrophic muscle, TN-C expression may be stimulated by the degenerative process and remain upregulated unless the tissue undergoes successful regeneration.
 ...
PMID:Tenascin-C expression in dystrophin-related muscular dystrophy. 855 62

Dystoroglycan is encoded by a single gene and cleaved into two proteins, alpha and beta-dystroglycan, by posttranslational processing. The 120kDa peripheral nerve isoform of alpha-dystroglycan binds laminin-2 comprised of the alpha 2, beta 1, and gamma 1 chains. In congenital muscular dystrophy and dy mice deficient in laminin alpha 2 chain, peripheral myelination is disturbed, suggesting a role for the dystroglycan- laminin interaction in peripheral myelinogenesis. To begin to test this hypothesis, we have characterized the dystroglycan-laminin interaction in peripheral nerve. We demonstrate that (1) alpha-dystroglycan is an extracellular peripheral membrane glycoprotein that links beta-dystroglycan in the Schwann cell outer membrane with laminin-2 in the endoneurial basal lamina, and (2) dystrophin homologues Dp116 and utrophin are cytoskeletal proteins of the Schwann cell cytoplasm. We also present data that suggest a role for glycosylation of alpha-dystroglycan in the interaction with laminin.
 ...
PMID:Characterization of dp6troglycan-laminin interaction in peripheral nerve. 862 7

Dinucleotide polymorphisms are short tandem repeat sequences that can be used as probes for haplotype analysis in Duchenne's muscular dystrophy (DMD). There are approximately a total of 50,000 to 100,000 such loci in the human genome, and they are highly informative due to the variability of allele lengths at these loci. Primers can be designed to amplify across such repeats located in the dystrophin gene to provide diagnostic information when RFLP analysis is uninformative. We report the usefulness of three such loci for analysis of DMD families in Singapore. The STR50 marker consists of (CA)n repeats located in intron 50 of the dystrophin gene while DYS1 marker is located upstream to the transcriptional start site for the brain dystrophin promoter and BSTRH marker is identified in the 3' untranslated region of the gene. End-labeled PCR products were resolved on 6% denaturing polyacrylamide sequencing gel. Alleles were identified by comparison with sequencing markers. PCR product typically ranged between 174 bp to 255 bp with five to six alleles observed. The heterozygosity rates estimated from 50 X chromosomes of unrelated individuals were 76.0% (BSTRH), 86.6% (DYS1) and 93.3% (STR50). In 38 DMD families studied, the results obtained show that these markers were highly informative and reveal Mendelian mode of inheritance. They were useful for linkage analysis, identification of deletion mutations, confirmation of paternity and mapping of gene recombination.
 ...
PMID:Usefulness of dinucleotide polymorphism markers in genetic analysis of Duchenne's muscular dystrophy cases in Singapore. 862 1

Dystrophin serves a variety of roles at the cell membrane through its associations, and defects in the dystrophin gene can give rise to muscular dystrophy and genetic cardiomyopathy. We investigated localization of cardiac dystrophin to determine potential intracellular sites of association. Subcellular fractionation revealed that while the majority of dystrophin was associated with the sarcolemma, about 35% of the 427-kDa form of dystrophin was present in the myofibrils. The dystrophin homolog utrophin was detectable only in the sarcolemmal membrane and was absent from the myofibrils as were other sarcolemmal glycoproteins such as adhalin and the sodium-calcium exchanger. Extraction of myofibrils with KC1 and detergents could not solubilize dystrophin. Dystrophin could only be dissociated from the myofibrillar protein complex in 5 M urea followed by sucrose density gradient centrifugation where it co-fractionated with one of two distinctly sedimenting peaks of actin. Immunoelectron microscopy of intracellular regions of cardiac muscle revealed a selective labeling of Z-discs by hystrophin antibodies. In the genetically determined cardiomyopathic hamster, strain CHF 147, the time course of development of cardiac insufficiency correlated with an overall 75% loss of myofibrillar dystrophin. These findings collectively show that a significant pool of the 427-kDa form of cardiac dystrophin was specifically associated with the contractile apparatus at the Z-discs, and its loss correlated with progression to cardiac insufficiency in genetic cardiomyopathy. The loss of distinct cellular pools of dystrophin may contribute to the tissue-specific pathophysiology in muscular dystrophy.
 ...
PMID:The association of cardiac dystrophin with myofibrils/Z-disc regions in cardiac muscle suggests a novel role in the contractile apparatus. 864 39

The dystrophin gene deletion patterns of Duchenne/Becker dystrophy were investigated in 57 DMD, 7 BMD and 1 DMD-BMD intermediate muscular dystrophy patients. Deletions, analyzed by multiplex amplification of selected exons, were observed in 58% (38 cases) of the patients. It was found that exon 48 was the most frequently affected, while exon 44 was the least frequently affected. The number of deleted exons was variable, but single exon deletions were more frequent (41%) than larger deletions in our population and the great majority of deletions began distal to exon 44. The application of PCR to deletion analysis in D/BMD was found to be very useful in delineating the extent of the deletion in most of the cases (82%). It was seen that the frequency of deletion breakpoints in distal part of the dystrophin gene (exons 42-52) was detected in 64% of our cases. In our group, the frequency of deletion breakpoints in the same area of the dystrophin gene was between that of the French and the Finnish patients. The distribution of deletion breakpoints within the dystrophin gene of the Turkish population seems to have some differences from other populations. Deletion breakpoints were found to be clustered mainly in three separate regions covering introns 44, 45 and 50 within the central region of the dystrophin gene. Intron 44 was mostly 5' breakpoints but it was found not to be involved as 3' breakpoints. The correlation between phenotype and type of deletion agreed with the reading frame theory except for one DMD case.
 ...
PMID:Molecular deletion patterns in Turkish Duchenne and Becker muscular dystrophy patients. 873 96

We report on a male patient aged 38, affected by a syndrome whose characteristic features include onset in early childhood, slow progression, diffuse muscle weakness, mental retardation and cardiomyopathy. Muscle biopsy showed myopathic changes compatible with muscular dystrophy. However, immunostaining for dystrophin as well as 50 and 43 kDa dystrophin-associated glycoproteins (DAGs) was normal. Genetic analysis suggested that direct involvement of the dystrophin gene was highly unlikely. No other family members were affected. Although the clinical picture is reminiscent of Duchenne/Becker muscular dystrophy, the immunologically and genetically documented lack of dystrophin involvement suggests that this particular syndrome is as yet undescribed.
 ...
PMID:Muscular dystrophy, mental retardation and cardiomyopathy not associated with dystrophin deficiency. 878 4

Duchenne muscular dystrophy (DMD) is an X-linked progressive muscle disorder which is caused by a defect of dystrophin, a 427-kDa muscle cell membrane protein. One of the possible means of DMD therapy is to express the dystrophin gene in patients' muscles. In this study, full length dystrophin cDNA was expressed in mdx (muscular dystrophy model) mouse muscle using the hemagglutinating virus of Japan (HVJ)-liposome method. With the HVJ-liposome method, the lacZ reporter genes were expressed in 50-80% of cultured mdx mouse myoblasts, which suggested its potential usefulness for an in vivo gene study. Three expression vectors containing human full length dystrophin cDNA driven by Rous sarcoma virus (RSV), mouse leukemia virus, or human dystrophin promoters, were used. HVJ-liposomes containing these plasmids were directly injected into mdx mouse quadriceps muscle. The highest efficiency of expression of dystrophin was in 26% of the muscle fibers at the injected site on day 3 after HVJ-liposome injection of the RSV-based vector. The expression was decreased on day 10. The study thus demonstrates the feasibility of full length human dystrophin cDNA transfer and dystrophin expression using HVJ-liposomes in vivo.
 ...
PMID:Expression of full-length human dystrophin cDNA in mdx mouse muscle by HVJ-liposome injection. 878 5

It has recently become possible to detect female carriers of Duchenne muscular dystrophy with no affected male relative in the family. These "isolated carriers" represent about 10% of women with high serum creatine phosphokinase (CPK) levels and clinical evidence of a muscle disease. Most isolated carriers ascertained by clinical and/or CPK levels and diagnosed by dystrophin immunostaining of muscle biopsy show symptoms of a muscular dystrophy, and often carry the diagnosis of recessive "limb-girdle muscular dystrophy" prior to dystrophin analysis. It has been difficult to offer genetic counseling and prenatal diagnosis for Duchenne muscular dystrophy in the families of these isolated carriers, largely due to the difficulty in determining which of the dystrophin alleles segregating in the family harbors the mutation in the heterozygote. Here we report genetic counseling of three isolated carriers and their families. In two cases, prenatal diagnosis of at-risk pregnancies was conducted. We determined X inactivation patterns and inheritance of X chromosomes in each family, and used this information to define the at-risk dystrophin gene. In all three families, the mutation was a de novo event, two in the paternal germ-line, and one in the maternal germ-line. In each case we show that sibs of the heterozygous woman are at population risk, while pregnancies of each propositus are at high risk. Our results show that accurate genetic counseling and prenatal diagnosis can be offered to these families.
 ...
PMID:Genetic counseling of isolated carriers of Duchenne muscular dystrophy. 882 37

We developed a Southern blotting based method that uses rare cutting restriction endonucleases and electrophoresis of single stranded DNA to detect junction fragments resulting from the rearranged dystrophin gene. By conventional Southern blot hybridisation, no junction fragments were detected in 27 unrelated patients with Duchenne (DMD) or Becker (BMD) muscular dystrophy, who had 20 deletions and seven duplications in the dystrophin gene. With our new method, junction fragments were detected in 21 of these 27 patients. When the junction fragments were used as markers, five carriers were unequivocally diagnosed among six females from two families of DMD/ BMD patients. This novel method allows simple and definitive identification of carriers with risk factors for DMD/BMD without using quantitative Southern blot hybridisation.
 ...
PMID:Identification of carriers of Duchenne/Becker muscular dystrophy by a novel method based on detection of junction fragments in the dystrophin gene. 900 37


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>