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

Duchenne's muscular dystrophy (DMD) is an X-linked progressive myopathy caused by a defect in the DMD gene locus. The gene corresponding to the DMD locus produces a 14-kilobase (kb) messenger RNA that codes for a large cytoskeletal membrane protein, dystrophin. DMD and Becker's muscular dystrophy are the consequences of dystrophin mutations. The exact biological function of dystrophin remains unknown but it has been demonstrated that it is localized to the cytoplasmic face of the cell membrane and has direct interaction with several other membrane proteins. We report here the synthesis of a 14-kb full-length complementary DNA for the mouse muscle dystrophin mRNA and the expression of this cDNA in COS cells. The recombinant dystrophin is indistinguishable from mouse muscle dystrophin by western blot analysis with anti-dystrophin antibodies and was shown by an immunofluorescent technique to be localized in the cell membrane. Our successful construction of a functional full-length cDNA opens opportunities for the study of structure and function of dystrophin and provides an opportunity to initiate gene therapy studies.
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PMID:Expression of recombinant dystrophin and its localization to the cell membrane. 182 97

Of the 3,048 diagnostic muscle biopsies processed by the National Institute of Neuroscience, Tokyo, over 12 years, 41 cases carried the clinical diagnosis of limb-girdle muscular dystrophy. We have analyzed all 41 cases for dystrophin content in muscle by both immunofluorescence and immunoblot. We identified five male patients with an abnormal dystrophin pattern diagnostic of Becker muscular dystrophy, and two female patients with dystrophin patterns consistent with a manifesting carrier of Duchenne muscular dystrophy diagnosis. Thus, 17% of our limb-girdle patients showed a dystrophinopathy, indicating that they in fact had a disorder related to Duchenne/Becker muscular dystrophy. Misclassification of isolated male limb-girdle patients was 31% (4/13), while misclassification of isolated female limb-girdle patients was 13% (2/15). Using multiplex polymerase chain reaction analyses of small amounts of muscle biopsy DNA confirmed a dystrophin gene deletion in all five male Becker dystrophy patients identified. This study emphasizes the clinical overlap between limb-girdle muscular dystrophy and dystrophinopathies, and reinforces the necessity of dystrophin protein and gene studies for the accurate clinical diagnosis of isolated cases of muscular dystrophy.
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PMID:The frequency of patients with dystrophin abnormalities in a limb-girdle patient population. 146 19

Neonatal screening for Duchenne/Becker Muscular dystrophy (DMD/BMD) was begun as a pilot program on January 1, 1986. The aim of this program was to reduce the incidence of this X-linked recessive degenerative neuromuscular disease. The neonatal detection of a boy with DMD allows early identification of carriers and genetic counselling. This may avert the birth of other affected males born prior to clinical diagnosis of DMD in the propositus at about age 5 years. Between January 1, 1986, and December 31, 1988, we identified and characterized a cohort of 8 asymptomatic infant boys with grossly elevated levels of creatine kinase, an active primary dystrophic process of muscle and complete dystrophin deficiency. Five of 8 males have detectable DNA alterations involving the DMD/BMD locus. Based on current hypotheses, characterization of dystrophin expression of this cohort allows us to predict a DMD phenotype in all 8 boys. To date, no additional males with DMD have been born in these families. Prospective follow-up will allow us to test the validity of dystrophin testing in predicting the clinical course and impact of this program on reproductive decision making in these families.
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PMID:Three years' experience with neonatal screening for Duchenne/Becker muscular dystrophy: gene analysis, gene expression, and phenotype prediction. 186 67

Two long-living brothers of dystrophin-related muscular dystrophy with an in-frame deletion of exon 3 of the dystrophin gene were described. Weakness of the lower extremities and pseudohypertrophy of calf muscles began at the age of 2 years in the elder brother and 4 years in the younger brother, respectively. Clinical symptoms progressed rapidly and both of them lost ambulation and became wheelchair bound at the age of 11-12 years. However, the progression of the disease process slowed in late teens, and now at the age of 36 and 33 years, respectively, they do not have respiratory or cardiac insufficiency, although they are disabled severely. Southern blotting with the entire dystrophin cDNAs, cDNA 1-2a, 2b-3, 4-5a, 5b-7, 8, and 9-14, revealed a single deletion of exon 3 in the 2 brothers. The mother was shown to be a heterozygote for this mutation. The unique clinical features of these brothers were presumed due to the following 2 factors: (1) a single deletion of exon 3 is an in-frame deletion of the dystrophin gene, and (2) exon 3 corresponds to a unique domain of the dystrophin molecule; the amino-terminal region which is highly homologous to the actin-binding-region of alpha-actinin. We consider that these 2 brothers are compatible with the so-called frame-shift hypothesis of Duchenne/Becker muscular dystrophy (DMD/BMD) phenotype, although they are diagnosed DMD by the classification method based on the patients' age of becoming permanently wheelchair bound.
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PMID:[Two long-living brothers of dystrophin-related muscular dystrophy with an in-frame deletion of exon 3 of the dystrophin gene--clinical features and diagnosis]. 189 67

Germ cell mosaics were demonstrated in Duchenne's and Becker's muscular dystrophy by molecular genetic methods. These findings affect risk estimates in these x-chromosomal muscular diseases. The mutation-selection equilibrium for x-chromosomally lethal inheritance for determining the a priori probability for risk estimate according to the Bayes theorem must therefore be redefined to take the germ cell mosaic problem into account. Taking Duchenne's and Becker's progressive muscular dystrophy as an example, the article explains how the estimation of the heterozygote risk in women seeking advice changes in different family situations.
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PMID:[Importance of germ cell mosaic for genetic counseling of families with Duchenne and Becker muscular dystrophy]. 194 41

Dystrophin is the gene product of the Duchenne (DMD) and Becker (BMD) muscular dystrophy gene locus on the short arm of the X chromosome. Complete lack of dystrophin is pathognomonic for DMD and variable changes of the molecule may be observed in the milder allelic form of BMD. In the present study the two methods available for dystrophin assessment, immunofluorescence detections on cryosections (IF) and Western blotting (WB) were systematically compared using polyclonal and monoclonal antibodies to various regions along the dystrophin molecule. A total of 95 patients with DMD or BMD were investigated including two female patients. Dystrophin assessment revealed abnormal abundance and/or distribution in all 95 patients with DMD or BMD. Only trace amounts of dystrophin were detected in 29% of the DMD patients and complete lack of dystrophin was found in 71%. In two females with DMD but with normal karyotype single dystrophin-positive fibres were found among more than 90% negative fibres. Out of 26 patients with BMD 19 (73%) had a dystrophin molecule of abnormal molecular weight. The results of IF were largely compatible with those from WB but differences were also observed, e.g. one barely symptomatic BMD patient with dystrophin of increased molecular weight showed normal IF. Out of four carriers of BMD three showed evidence of reduced dystrophin immunostaining in some muscle fibres. In 20 other patients limb girdle muscualar dystrophy with "Duchenne-like" or "Becker-like" phenotype was suspected because dystrophin showed normal abundance and distribution. Focal discontinuity of muscle cell-surface dystrophin staining was observed in one patient with a congenital, autosomal recessive muscular dystrophy and in one out of five patients with polymyositis/dermatomyositis. The study emphasizes the need for, and value of, dystrophin assessment in every case of suspected BMD or DMD.
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PMID:Dystrophin as a diagnostic marker in Duchenne and Becker muscular dystrophy. Correlation of immunofluorescence and western blot. 194 22

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive disorder of muscle in children, with an incidence of approximately 1 in 3,300 male births. In about a third of affected boys, the disease is due to a new mutation, and most patients die in their early 20s. Over the last few years, the genetic, biochemical and histopathological basis of DMD has been elucidated greatly. In particular, the discovery of "dystrophin," the protein product of the DMD gene is truly an epoch-making success in the history of muscular dystrophy research. Dystrophin is now thought to be a cytoskeletal protein underlying the plasma membrane (known in muscle as the sarcolemma) of normal muscle fiber, and is undetectable or greatly reduced in DMD. In this review article, dystrophin in normal skeletal muscle and various neuromuscular diseases including DMD/BMD (Becker muscular dystrophy), and its carrier is discussed.
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PMID:Dystrophin abnormality in progressive muscular dystrophy--a review article. 195 48

In an isolated male patient, differentiation between Facio-Scapulo-Humeral Muscular Dystrophy (FSH) and Becker Muscular Dystrophy (BMD) may be difficult. To emphasise this point, we report a patient, whose features are atypical of FSH. Details of his daughter who now manifests similar presenting features, are provided. The pitfalls posed for the genetic counsellor by FSH presenting in an atypical manner which clinically overlaps with genetically distinct conditions are discussed in the light of this pedigree.
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PMID:Atypical facio-scapulo-humeral muscular dystrophy--a counselling dilemma. 827 79

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

We report on 5 brothers with slowly progressive limbgirdle weakness. Calf hypertrophy was absent. The levels of creatine kinase, electromyography, and findings from a muscle biopsy specimen were compatible with muscular dystrophy. The propositus's biopsy specimen also showed numerous rimmed vacuoles. DNA analysis revealed a deletion in the dystrophin gene, establishing a diagnosis of Becker muscular dystrophy. Both the absence of calf hypertrophy and the presence of rimmed vacuoles are unusual features in this disorder.
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PMID:An unusual variant of Becker muscular dystrophy. 219 11


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