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

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

Using 10 overlapping nested sets of primers and using peripheral blood lymphocyte (PBL) total RNA as template, we have developed a system, based on PCR, which allows the rapid production of double-stranded cDNA corresponding to the entire coding sequence of the dystrophin gene. The product can be visualized on native minigels by ethidium staining and directly sequenced after gel purification. We have used this system to analyze the structures of PBL dystrophin mRNA in 26 Duchenne, Becker, or intermediate muscular dystrophy patients who have gross rearrangements of the dystrophin gene. In each case, the effect that the genomic rearrangement has on the structure of the transcript--and, by inference, on the dystrophin protein--has been determined, and the results confirm the frameshift hypothesis. The study also identifies a series of alternatively spliced transcripts which are specific to the rearranged genotypes and which seem therefore to arise following the alteration in the context of the splice signal. The system has been used for unambiguous identification of carrier females. Furthermore, the rapid production of microgram quantities of dystrophin cDNA from a readily accessible tissue makes point-mutation screening a practical proposition.
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PMID:Direct detection of dystrophin gene rearrangements by analysis of dystrophin mRNA in peripheral blood lymphocytes. 186 92

Duchenne's muscular dystrophy (DMD), which affects one in 3,500 males, causes progressive myopathy of skeletal and cardiac muscles and premature death. One approach to treatment would be to introduce the normal dystrophin gene into diseased muscle cells. When pure plasmid DNA is injected into rodent skeletal or cardiac muscle, the cells express reporter genes. We now show that a 12-kilobase full-length human dystrophin complementary DNA gene and a 6.3-kilobase Becker-like gene can be expressed in cultured cells and in vivo. When the human dystrophin expression plasmids are injected intramuscularly into dystrophin-deficient mdx mice, the human dystrophin proteins are present in the cytoplasm and sarcolemma of approximately 1% of the myofibres. Myofibres expressing human dystrophin contain an increased proportion of peripheral nuclei. The results indicate that transfer of the dystrophin gene into the myofibres of DMD patients could be beneficial, but a larger number of genetically modified myofibres will be necessary for clinical efficacy.
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PMID:Human dystrophin expression in mdx mice after intramuscular injection of DNA constructs. 188 32

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

In this brief review, we describe the clinical manifestations of Duchenne's muscular dystrophy (DMD) and other similar syndromes, outline the history of the dystrophin gene's identification and its relationship to these muscular dystrophies, and relate the importance of the gene's discovery to clinical neurology. We do not discuss treatment.
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PMID:Duchenne's muscular dystrophy: review and recent scientific findings. 189 57

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

We have characterized deletions of the dystrophin gene in patients suffering from relatively mild muscular dystrophy. Our data show that most of the Becker muscular dystrophy (BMD) patients have intragenic deletions which leave the protein reading frame in phase. Remarkably, large deletions of the region corresponding to the central triple helical repeats in the protein can result in an exceptionally mild phenotype. Three brothers suffering from BMD, glycerol kinase deficiency, and adrenal hypoplasia possess a deletion at the 3' end of the gene. They also display developmental delay. Thus the 3' processing of the gene must be necessary for the correct function of the dystrophin molecule.
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PMID:Characterization of deletions in the dystrophin gene giving mild phenotypes. 224 31

DMD and BMD are now understood at the genetic, biochemical, and molecular levels. At the genetic level, both disorders result from mutations of the X-linked gene encoding dystrophin. At the biochemical level, DMD results from the deficiency of a large protein called dystrophin, whereas BMD results when dystrophin is present, though abnormal in either amount or molecular structure. To date, thousands of patients have been analyzed for mutations of the dystrophin gene in peripheral blood DNA or alterations of the dystrophin protein in muscle tissue. The severity of the clinical phenotype of these patients has been compared with their dystrophin gene mutations and corresponding dystrophin protein alterations, revealing an unexpectedly high degree of correlation. Thus, information derived from the molecular analysis (DNA or protein) of a particular patient provides a "molecular diagnosis," which is highly predictive of the clinical course that patient can be expected to follow. Because molecular diagnoses are independent of the patient's age, they provide a prognosis for the large majority of muscular dystrophy patients even before clinical symptoms of their disease become apparent. Such prognostic molecular diagnoses have proven particularly valuable when the patient is an isolated case, with no family history for the disorder. Prenatal genetic diagnosis of DMD or BMD may involve use of Southern blot or PCR techniques to search for a deletion in the DNA of at-risk fetuses or more complicated family linkage studies using intragenic and flanking RFLPs. More recently, assay of dystrophin content in fetal skeletal or cardiac muscle from at-risk abortuses has been accomplished, allowing definitive discrimination of affected and normal fetuses in cases in which deletion analyses and family DNA studies were equivocal. In utero fetal skeletal muscle biopsy for dystrophin protein assay has actually been accomplished in at least one at-risk pregnancy in which family DNA studies were uninformative. Dystrophin was present in skeletal muscle from this 20-week-old male fetus, and the pregnancy continued, resulting in the term birth of a healthy male infant. The future holds exciting opportunities for neonatal screening and treatment of these devastating neuromuscular diseases.
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PMID:Duchenne and Becker muscular dystrophies: genetics, prenatal diagnosis, and future prospects. 228 31

The similarity in clinical features of X-linked Becker muscular dystrophy (BMD) and the autosomal recessive limb-girdle (LGD) type of adult muscular dystrophy makes differential diagnosis of the isolated male case difficult. DNA probes complementary (cDNA) to the Duchenne/Becker muscular dystrophy gene product, dystrophin, can detect molecular deletions in 60-70% of affected subjects. Thirty-three patients with BMD or LGD (thirty isolated and three with an affected brother) were screened with a panel of cDNA probes for the whole dystrophin gene. Deletions were found in thirteen of eighteen (72%) patients with a diagnosis of BMD. Deletions were also found in four of the fifteen (27%) patients previously thought to have LGD, who were therefore reclassified as having BMD. All male patients with progressive muscular dystrophy of limb-girdle pattern should be routinely screened with these cDNA probes as a useful adjunct to their clinical diagnosis since the results have important implications for genetic counselling of affected families.
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PMID:Distinction of Becker from limb-girdle muscular dystrophy by means of dystrophin cDNA probes. 256 42

An autosomal recessive (AR) form of muscular dystrophy that clinically resembles Duchenne/Becker types exists, but its frequency is unknown. We have studied three unrelated affected brother/sister pairs and their families for deletions and polymorphisms with the entire dystrophin cDNA and other DNA probes from the Xp21 region to test for involvement of the DMD locus. In family 1 a large intragenic deletion was found in the affected male. The affected sister was heterozygous for this deletion, but the mother was not, implying germinal mosaicism. In family 2, no deletion was detected in the affected male. RFLP analysis revealed that the affected male and an unaffected sister shared a complete Xp21 haplotype while the affected sister had inherited a recombinant Xp21 region resulting from a crossover between pERT 87-15 and J-Bir. Only the 5' region of the dystrophin gene was shared with the affected boy. X-inactivation studies using a polymorphism in the 5'-flanking region of the HPRT gene, in conjunction with methylation-sensitive enzymes, revealed random X inactivation in the affected girl's leukocytes. In a muscle biopsy from the affected male, the dystrophin protein was present in normal amount and size. Family 3 was informative for four RFLPs detected with dystrophin cDNA probes which span the entire gene. The affected male was found to share the complete dystrophin RFLP haplotype with his unaffected brother, while his affected sister had inherited the other maternal haplotype. It is concluded that the clinical presentation of early-onset, progressive muscular dystrophy in a male and in his karyotypically normal sister can be caused by mutations at different loci. While in family 1 a deletion in the dystrophin gene is responsible, this gene does not appear to be involved in families 2 and 3.
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PMID:Brother/sister pairs affected with early-onset, progressive muscular dystrophy: molecular studies reveal etiologic heterogeneity. 256 91


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