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

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

An isolated case of Duchenne muscular dystrophy (DMD) in a female who has a deletion of the DMD locus is described. This patient was a 26-year-old woman born to unrelated, healthy parents. She was initially examined at age 6 because of a waddling gait. At age 15, pseudohypertrophy of calves and pes equinus were observed along with proximal muscular weakness and wasting. Her serum creatine kinase level was high and histological evidence of muscular dystrophy was apparent on muscle biopsy. The patient was ambulant at age 15 and progression of motor disability has been slow. Chromosomal studies revealed a normal karyotype, and mental retardation is moderate. DNA analysis at age 26 revealed that she has a deletion of DMD cDNA 8 mapped within Xp21 and is heterozygous for the deletion. Since diagnosis of DMD is now dependent on the evidence of mutation or deletion at Xp21, this patient is thought to have a form of DMD. Expression of the DMD gene in the heterozygous state might be due to random but unequal lyonization.
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PMID:An isolated case of Duchenne muscular dystrophy (DMD) in a female with a deletion of DMD cDNA. 228 21

Gross pathologic lesions and light microscopic and ultrastructural features of skeletal muscle lesions in canine X-linked muscular dystrophy (CXMD) were studied in dogs from 3 months to 6 years of age. Necrosis and regeneration were present at all ages, but were most prominent in the youngest dogs studied. Increased intracytoplasmic calcium, as evidenced by positive alizarin red S staining, was associated with fiber necrosis, but was also seen in small numbers of otherwise normal fibers. Progressive changes included development of severe fiber size variation, endomysial and perimysial fibrosis, prominent cytoplasmic disorganization, internalization of myonuclei, mitochondrial proliferation, mild fat infiltration, and alterations in the fiber-type pattern. The most consistent early ultrastructural changes were dilatation of the sarcoplasmic reticulum and focal subsarcolemmal areas of degeneration. Convincing sarcolemmal defects were not found. Z-band streaming was present at all ages, and Z-band duplication and nemaline rods were seen in older dogs. Evidence for abnormal regeneration was found in the oldest dog, and was associated with extensive fibrosis. These findings document the progression of lesions in CXMD, and illustrate the profound alterations in fiber organization and fiber type that may occur in late stages of dystrophin-deficient muscular dystrophy.
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PMID:Canine X-linked muscular dystrophy: morphologic lesions. 237 May 57

An 8 year-old female infant with the clinical and pathological characteristics of both progressive muscular dystrophy and mitochondrial myopathy was described. Her maternal cousin had clinical and pathological findings of Duchenne muscular dystrophy (DMD). Since the patient had markedly elevated serum CK and calf muscle hypertrophy, her muscle was biopsied and she was diagnosed as having female DMD at the age of 5 years. She had generalized tonic-clonic convulsions and alternate hemiconvulsions for recent 4 years which brought her our hospital. On admission, she had mild generalized muscle atrophy and weakness predominantly in the proximal limbs. The lactate and pyruvate levels in both serum and cerebrospinal fluid were elevated, but with no metabolic acidosis. Serum CK was elevated to 4464 IU/L. Brain CT and MRI showed the expanding arachnoid cyst in the left middle fossa of cranium. In the biopsied left biceps crachii muscle, in addition to numerous ragged-red fibers, there were active muscular fiber necrosis and regeneration and interstitial fibrosis similar to those seen in progressive muscular dystrophy. Biochemically, no decrease or defect in the respiratory chain enzymes was detected. On electron microscopy, a large number of fibers contained aggregates of giant mitochondria with proliferated complicated cristae. Scattered throughout were necrotic muscle fibers filled with phagocytes and regenerating fibers. This patient had the diagnostic features of mitochondrial encephalomyopathy and progressive muscular dystrophy. We supposed that the patient provided very interesting evidences to study the relationship between mitochondrial myopathy and progressive muscular dystrophy.
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PMID:[A female infant of mitochondrial myopathy with findings of active necrosis and regeneration of muscle fibers]. 238 14

Serum levels of selenium and vitamin E were prospectively studied in children with Duchenne de Boulogne muscular dystrophy of variable age and muscular status. In contrast with previous studies, we found no differences with controls. However, we believe that selenium and vitamin E, two natural antioxydants, may contribute to the pathophysiology of pseudohypertrophic muscular dystrophy. A study of the effects of supplementation is on-going.
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PMID:[Selenium and vitamin E in patients with progressive muscular dystrophy]. 240 Jan 91

Emery-Dreifuss muscular dystrophy is sometimes referred to as benign X-linked muscular dystrophy. We present two young patients with this disorder who had severe cardiovascular complications including: conduction disease, major thromboembolic events, valvular dysfunction with congestive cardiac failure, ventricular tachyarrhythmias, and sudden cardiac death. Of these cardiac problems, only conduction disease has been previously emphasized. This form of muscular dystrophy is not benign--it has malignant cardiac manifestations.
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PMID:Benign X-linked (Emery-Dreifuss) muscular dystrophy is not benign. 244 2

In patients with Duchenne muscular dystrophy (DMD), heart failure appears in later stage of the disease due to myocardial degeneration and respiratory insufficiency, and sometimes causes death. However, there have been no adequate parameters which can be used easily to evaluate the grade of heart failure in DMD, except cardiac enlargement and pulmonary congestion observed by chest X-ray picture. Thus, we measured the plasma concentrations of atrial natriuretic peptide (ANP) in the patients with muscular dystrophy of various types, and studied a relationship between plasma ANP concentration and heart failure, expecting that it could be an index of heart failure in DMD patients. The plasma ANP concentrations in patients with DMD were 35.5 +/- 3.3pg/ml (mean +/- SE) and higher than in normal subjects (19.3 +/- 1.0pg/ml). In the patients with limb-girdle muscular dystrophy, facioscapulohumeral muscular dystrophy and neurogenic muscular atrophy, the plasma ANP concentration showed a tendency to elevate. However, no elevation of plasma ANP levels was observed in the patients with other types of muscular dystrophy. In DMD, number of the patients having a high plasma ANP concentration was increased with progress of disability grade, and decrease in serum creatine kinase activity and serum myoglobin concentration. There was a significant correlation (p less than 0.01) between plasma ANP concentration and cardiothoracic ratio or PEP/LVET, but no correlation between the concentration and respiratory failure. Immunohistochemistry of the atrial cardiac muscle of an autopsied DMD case revealed many ANP-positive atrial muscle cells, indicating the preservation of ANP-secreting function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Secretion and clinical significance of atrial natriuretic peptide in patients with muscular dystrophy]. 252 1

We studied selenium metabolism in patients with Duchenne muscular dystrophy and in contrast to previous reports found no significant abnormalities in these patients. Supplementation of muscular dystrophy patients and control subjects with sodium selenite (1 mg selenium/day) induced a variable rise in the activity of the selenium-dependent enzyme glutathione peroxidase in plasma and red cells, but no significant change in muscle glutathione peroxidase activities. There was no effect of selenium supplementation on disease activity in the patients with muscular dystrophy. Thiobarbituric acid-reacting substances (an index of free radical-mediated lipid peroxidation) were elevated in the muscle of patients with Duchenne muscular dystrophy in contrast to patients with other forms of muscular dystrophy and control subjects. This elevation was unaffected by selenium supplementation.
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PMID:Selenium metabolism and supplementation in patients with muscular dystrophy. 254 Apr 51

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

Most known mutations in the gene region responsible for Duchenne or Becker muscular dystrophy are deletions of varying extent. Here we describe a 220-kb insertion within the DMD/BMD gene that cosegregates with a somewhat atypical course of muscular dystrophy in a pedigree. The insertion is demonstrated by field-inversion gel electrophoresis as an enlarged SfiI fragment hybridizing to probe J-Bir, while neighboring SfiI fragments (detected by probes PERT 87 and J-66) are unchanged. Hybridization with DMD c-DNA probes did not reveal alterations in coding sequences. In this pedigree, the altered SfiI fragments provide convenient markers for carrier identification.
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PMID:Identification of a 220-kb insertion into the Duchenne gene in a family with an atypical course of muscular dystrophy. 256 31


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