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

The pathogenesis of dilated cardiomyopathy in Emery- Dreifuss muscular dystrophy (EDMD) is still unknown. Autoimmune mechanisms have recently been taken into account. The aim of this investigation was to determine whether the level of circulating antibodies to heart proteins which were previously detected, correlates with disease progression. Troponin I was chosen as the target. Ten patients with EDMD and 10 age-matched normal controls were tested. An enzyme linked immunoassay (ELISA) technique was used to determine the possible relation between the level of anti-troponin I antibodies at diagnosis and at followup. Autoantibodies against troponin I were detected in all EDMD patients. At diagnosis the level was higher in the X-linked EDMD form (X-EDMD), as compared to the autosomal dominant form (AD-EDMD). At follow-up the elevated level of the autoantibodies persisted in all the EDMD cases. However, in the AD-EDMD form, the level was found to be significantly rising with disease progression, in the X-EDMD form, on the other hand, it was declining. No clear-cut relationship between the level of the circulating antibodies and cardiac symptomatology was present. Detection of anti-troponin I antibodies may provide a non-invasive marker of early stages of dilated cardiomyopathy in EDMD.
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PMID:Circulating autoantibodies to troponin I in Emery-Dreifuss muscular dystrophy. 1910 70

Emery-Dreifuss muscular dystrophy (EDMD) is a rare disorder characterized by early joint contractures, muscular dystrophy, and cardiac involvement with conduction defects and arrhythmias. So far, only 35% of EDMD cases are genetically elucidated and associated with EMD or LMNA gene mutations, suggesting the existence of additional major genes. By whole-genome scan, we identified linkage to the Xq26.3 locus containing the FHL1 gene in three informative families belonging to our EMD- and LMNA-negative cohort. Analysis of the FHL1 gene identified seven mutations, in the distal exons of FHL1 in these families, three additional families, and one isolated case, which differently affect the three FHL1 protein isoforms: two missense mutations affecting highly conserved cysteines, one abolishing the termination codon, and four out-of-frame insertions or deletions. The predominant phenotype was characterized by myopathy with scapulo-peroneal and/or axial distribution, as well as joint contractures, and associated with a peculiar cardiac disease characterized by conduction defects, arrhythmias, and hypertrophic cardiomyopathy in all index cases of the seven families. Heterozygous female carriers were either asymptomatic or had cardiac disease and/or mild myopathy. Interestingly, four of the FHL1-mutated male relatives had isolated cardiac disease, and an overt hypertrophic cardiomyopathy was present in two. Expression and functional studies demonstrated that the FHL1 proteins were severely reduced in all tested patients and that this was associated with a severe delay in myotube formation in the two patients for whom myoblasts were available. In conclusion, FHL1 should be considered as a gene associated with the X-linked EDMD phenotype, as well as with hypertrophic cardiomyopathy.
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PMID:Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy. 1971 12

We have performed a detailed population study of patients with genetic muscle disease in the northern region of England. Our current clinic population comprises over 1100 patients in whom we have molecularly characterized 31 separate muscle disease entities. Diagnostic clarity achieved through careful delineation of clinical features supported by histological, immunological and genetic analysis has allowed us to reach a definitive diagnosis in 75.7% of our patients. We have compared our case profile with that from Walton and Nattrass' seminal study from 1954, also of the northern region, together with data from other more recent studies from around the world. Point prevalence figures for each of the five major disease categories are comparable with those from other recent studies. Myotonic dystrophies are the most common, comprising 28.6% of our clinic population with a point prevalence of 10.6/100,000. Next most frequent are the dystrophinopathies and facioscapulohumeral muscular dystrophy making up 22.9% (8.46/100,000) and 10.7% (3.95/100,000) of the clinic population, respectively. Spinal muscular atrophy patients account for 5.1% or 1.87/100,000 patients. Limb girdle muscular dystrophy, which was described for the first time in the paper by Walton and Nattrass (1954) and comprised 17% of their clinic population, comprises 6.2% of our clinic population at a combined prevalence of 2.27/100,000. The clinic population included patients with 12 other muscle disorders. These disorders ranged from a point prevalence of 0.89/100 000 for the group of congenital muscular dystrophies to conditions with only two affected individuals in a population of three million. For the first time our study provides epidemiological information for X-linked Emery-Dreifuss muscular dystrophy and the collagen VI disorders. Each of the X-linked form of Emery-Dreifuss muscular dystrophy and Ullrich muscular dystrophy has a prevalence of 0.13/100,000, making both very rare. Bethlem myopathy was relatively more common with a prevalence of 0.77/100,000. Overall our study provides comprehensive epidemiological information on individually rare inherited neuromuscular conditions in Northern England. Despite the deliberate exclusion of relatively common groups such as hereditary motor and sensory neuropathy (40/100,000) and mitochondrial disorders (9.2/100,000), the combined prevalence is 37.0/100,000, demonstrating that these disorders, taken as a group, encompass a significant proportion of patients with chronic disease. The study also illustrates the immense diagnostic progress since the first regional survey over 50 years ago by Walton and Nattrass.
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PMID:Prevalence of genetic muscle disease in Northern England: in-depth analysis of a muscle clinic population. 1976 15

Although Duchenne muscular dystrophy is primarily classified as a neuromuscular disease, cardiac complications play an important role in the course of this X-linked inherited disorder. The pathobiochemical steps causing a progressive decline in the dystrophic heart are not well understood. We therefore carried out a fluorescence difference in-gel electrophoretic analysis of 9-month-old dystrophin-deficient versus age-matched normal heart, using the established MDX mouse model of muscular dystrophy-related cardiomyopathy. Out of 2,509 detectable protein spots, 79 2D-spots showed a drastic differential expression pattern, with the concentration of 3 proteins being increased, including nucleoside diphosphate kinase and lamin-A/C, and of 26 protein species being decreased, including ATP synthase, fatty acid binding-protein, isocitrate dehydrogenase, NADH dehydrogenase, porin, peroxiredoxin, adenylate kinase, tropomyosin, actin, and myosin light chains. Hence, the lack of cardiac dystrophin appears to trigger a generally perturbed protein expression pattern in the MDX heart, affecting especially energy metabolism and contractile proteins.
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PMID:Proteomic Profiling of the Dystrophin-Deficient MDX Heart Reveals Drastically Altered Levels of Key Metabolic and Contractile Proteins. 2050 50

Duchenne muscular dystrophy (DMD) is an X-linked form of muscular dystrophy characterized by progressive limb-girdle distribution of muscle weakness. Morbidity related to cardiomyopathy (CMO) is common, but cerebral infarction (CI) is relatively rare in these patients. We report a case of a pontine infarct in a patient with DMD and advanced CMO, and review the published data on CMO and CI in patients with DMD.
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PMID:Cerebral infarction in Duchenne muscular dystrophy. 2062 21

Duchenne muscular dystrophy (DMD) is an X-linked, progressive muscle-wasting disease caused by mutations in the DMD gene. Since the disease was described by physicians in the 19th century, information about the subject has been accumulated. One author (Sugita) was one of the coworkers who first reported that the serum creatine kinase (CK) level is elevated in progressive muscular dystrophy patients. Even 50 years after that first report, an elevated serum CK level is still the most useful marker in the diagnosis of DMD, a sensitive index of the state of skeletal muscle, and useful to evaluate therapeutic effects. In the latter half of this article, we describe recent progress in the therapy of DMD, with an emphasis on gene therapies, particularly exon skipping.
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PMID:Progress in muscular dystrophy research with special emphasis on gene therapy. 2068 32

Duchenne muscular dystrophy (DMD) is a severe recessive X-linked form of muscular dystrophy caused by mutations in the dystrophin gene and it affects males predominantly. Here we report a 4-year-old girl with DMD from a healthy family, in which her parents and sister have no DMD genotype. A PCR-based method of multiple ligation-dependent probe amplification (MLPA) analysis showed the deletion of exons 46 and 47 in the dystrophin gene, which led to loss of dystrophin function. No obvious phenotype of Turner syndrome was observed in this patient and cytogenetic analysis revealed that her karyotype is 46,X,i(X)(q10). In conclusion, we describe the first female patient with DMD who carries a de novo mutation of the dystrophin gene in one chromosome and isochromosome Xq, i(Xq), in another chromosome.
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PMID:Duchenne muscular dystrophy in a female patient with a karyotype of 46,X,i(X)(q10). 2094 43

Duchenne muscular dystrophy (DMD) is the most common, lethal, X-linked genetic disease, affecting 1 in 3500 newborn males. It is caused by mutations in the DMD gene. Owing to the large size of the gene, the mutation rate in both germline and somatic cells is very high. Nearly 13-15% of DMD cases are caused by nonsense mutations leading to premature termination codons in the reading frame that results in truncated dystrophin protein. Currently there is no cure for DMD. The only available treatment is the use of glucocorticoids that have modest beneficial effects accompanied by significant side effects. Different therapeutic strategies have been developed ranging from gene therapy to exon skipping and nonsense mutation suppression to produce the full-length protein. These strategies have shown promise in the mdx mouse model of muscular dystrophy where they have been reported to ameliorate the dystrophic phenotype and correct the physiological defects in the membrane. Each of these molecular approaches are being investigated in clinical trials. Here we review nonsense mutation suppression by aminoglycosides as a therapeutic strategy to treat DMD with special emphasis on gentamicin-induced readthrough of disease-causing premature termination codons.
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PMID:Aminoglycoside-induced mutation suppression (stop codon readthrough) as a therapeutic strategy for Duchenne muscular dystrophy. 2117 98

Duchenne muscular dystrophy, the most common form of childhood muscular dystrophy, is caused by X-linked inherited mutations in the dystrophin gene. Dystrophin deficiencies result in the loss of the dystrophin-glycoprotein complex at the plasma membrane, which leads to structural instability and muscle degeneration. Previously, we induced muscle-specific overexpression of Akt, a regulator of cellular metabolism and survival, in mdx mice at pre-necrotic (<3.5 weeks) ages and demonstrated upregulation of the utrophin-glycoprotein complex and protection against contractile-induced stress. Here, we found that delaying exogenous Akt treatment of mdx mice after the onset of peak pathology (>6 weeks) similarly increased the abundance of compensatory adhesion complexes at the extrasynaptic sarcolemma. Akt introduction after onset of pathology reverses the mdx histopathological measures, including decreases in blood serum albumin infiltration. Akt also improves muscle function in mdx mice as demonstrated through in vivo grip strength tests and in vitro contraction measurements of the extensor digitorum longus muscle. To further explore the significance of Akt in myofiber regeneration, we injured wild-type muscle with cardiotoxin and found that Akt induced a faster regenerative response relative to controls at equivalent time points. We demonstrate that Akt signaling pathways counteract mdx pathogenesis by enhancing endogenous compensatory mechanisms. These findings provide a rationale for investigating the therapeutic activation of the Akt pathway to counteract muscle wasting.
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PMID:Myogenic Akt signaling attenuates muscular degeneration, promotes myofiber regeneration and improves muscle function in dystrophin-deficient mdx mice. 2124 83

Genetic counselling of two younger sisters of a 32-year-old man with a 28-year history of severe progressive muscular dystrophy stimulated efforts to determine his diagnosis and the mode of inheritance. The investigation was complicated by the patient's sudden death during the period of investigation. However, genetic and neurological evaluation, electromyography and nerve conduction studies, serum enzymes and reinterpretation of a muscle biopsy 23 years earlier made it unlikely that inheritance was X-linked, thereby substantially reducing his sisters' risk of bearing affected children. Precise diagnosis, especially of what is not likely in atypically presenting genetic disease, is of paramount importance in managing families at risk for genetic disease in future children. It is an important responsibility of family physicians concerned with preventive genetic medicine.
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PMID:Atypical severe muscular dystrophy in a male: genetic implications for female relatives. 2127 60


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