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

X-linked dominant inheritance with lethality in hemizygous males is a rare mode of inheritance. The three best-known disorders which seem to be inherited in this way, are incontinentia pigmenti (IP) Bloch-Sulzberger, oral-facial-digital I (OFD I) syndrome, and focal dermal hypoplasia (FDH syndrome, Goltz syndrome). It is the purpose of this article to give a review of the clinical and genetic aspects of the above-mentioned diseases and to add those disorders in which this mode of inheritance is discussed. These disorders are: X-linked chondrodysplasia punctata (CP), cervico-oculo-acusticus syndrome (Wildervanck syndrome, COA), congenital cataract with microcornea or slight microphthalmia, muscular dystrophy--hemizygous lethal, partial lipodystrophy with lipatrophic diabetes and hyperlipidemia, Aicardi syndrome, coxo-auricular syndrome, and Johanson-Blizzard syndrome. OTC deficiency is included in the study, although there is no lethality in utero, only in the neonatal period. A critical evaluation of the current literature is carried out.
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PMID:X-linked dominant inherited diseases with lethality in hemizygous males. 687 41

Content of hypophysis-, adrenal gland- and thyroid gland-tropic hormones was studied in blood plasma of children with primary X-linked Dushenne's myopathy at various periods of the disease, as compared with the patterns observed in healthy children of the same age. Increase in the functional activity of hypophysis and decrease -- in functions of adrenal cortex glands were observed in the muscular dystrophy; these alterations correlated with the disease steps. Relationship between the hormonal alterations and the dystrophy steps suggests the importance of the hormones in pathogenesis of the myodystrophic impairment.
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PMID:[Content of hypophysiotropic, adrenotropic and thyrotropic hormones in the blood in Duchenne's progressive muscular dystrophy]. 711 51

The fantastic advances in fundamental research into muscular dystrophy over the past few years have led to the discovery of a cytoskeleton protein called dystrophin and a group of associated and analogous molecules. The understanding of their molecular structure and the modes of genetic and functional regulation have forced us to take a new look at our concept of the pathogenesis of muscular dystrophy. Today, the group of diseases called X-linked hereditary muscular dystrophies must now be conceived in light of a deficiency in dystrophin. The exact physiopathology of the process involved is not yet fully understood but most undoubtedly, although the lack of dystrophin can trigger the disease, the deficiency cannot in itself impede muscle contraction. As a result of these discoveries, diagnostic methods have changed drastically, genetic counselling has become more precise, and most importantly, new treatment rationales can call upon pharmacological processes capable of stopping disease progression. Genetic therapy is another approach. The aim is to provide the deficient cells with the capacity of synthesizing normal dystrophin or an analogous molecule, thus halting the cascade of events leading to necrosis. The transfer of the technical means which have made these fundamental advances in basic research possible to successful clinical applications in the treatment of muscular dystrophy will be another of the lessons to be learned from dystrophin.
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PMID:[Lessons of dystrophin]. 793 19

Duchenne and Becker muscular dystrophies are caused by defects of the dystrophin gene. Expression of this large X-linked gene is under elaborate transcriptional and splicing control. At least five independent promoters specify the transcription of their respective alternative first exons in a cell-specific and developmentally controlled manner. Three promoters express full-length dystrophin, while two promoters near the C terminus express the last domains in a mutually exclusive manner. Six exons of the C terminus are alternatively spliced, giving rise to several alternative forms. Genetic, biochemical and anatomical studies of dystrophin suggest that a number of distinct functions are subserved by its great structural diversity. Extensive studies of dystrophin may lead to an understanding of the cause and perhaps a rational treatment for muscular dystrophy.
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PMID:The structural and functional diversity of dystrophin. 798 47

Golden retriever muscular dystrophy (GRMD) is an X-linked myopathy homologous with Duchenne muscular dystrophy of human beings. Affected dogs have progressive clinical dysfunction due to muscle wasting and contractures. Deficits progress particularly rapidly between 3 and 6 months of age. To better characterize the role of contractures in this deterioration, the flexor surface, nonweight-bearing tarsal joint angle was measured in GRMD-affected dogs and clinically normal littermates at both ages. The mean +/- SD tarsal joint angle for clinically normal dogs decreased from 164.6 +/- 6.09 degrees to 145.6 +/- 8.80 degrees between 3 and 6 months (P < 0.0005). The value for GRMD-affected dogs decreased from 153.3 +/- 11.44 degrees to 117.6 +/- 24.55 degrees (P < 0.005). The angle for clinically normal dogs was greater than that for GRMD-affected dogs at both ages (P < 0.05 at 3 months and P < 0.01 at 6 months). The decrease in tarsal joint angle, at times to less than 90 degrees, correlated well with other phenotypic features of GRMD, such as loss of the ability to walk.
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PMID:Tarsal joint contracture in dogs with golden retriever muscular dystrophy. 798 43

Golden Retriever dogs manifest an X-linked, Duchenne-like, muscular dystrophy with a characteristic lack of dystrophin. Histologic findings have demonstrated the cardiac involvement in these dogs to be a model for the cardiac insufficiency in human Duchenne muscular dystrophy (DMD). The goal of this study was to assess the capability of radionuclide angiography (RNA) as an assessment tool to measure the ventricular dysfunction in these dogs. Three dogs, one normal and two with muscular dystrophy (MD), were studied by equilibrium gated blood pool. Red blood cells were labelled with 420 MBq of 99mTc. The three dogs lying on their left sides on the table, received no drugs and were not restrained in any manner. RNA left ejection fraction (EF) and echographic measurements of left ventricular fractional shortening (FS) were performed during the same session. EF values were 61%, 48%, 36% and FS values were 47%, 32%, 26%, respectively, for the control dog, the 6 month old MD dog and the 12 month old MD dog. This preliminary study demonstrates the potential usefulness of RNA for the non-invasive follow-up exams of specific therapy in a canine model of muscular dystrophy.
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PMID:Non-invasive evaluation of the cardiac function in golden retriever dogs by radionuclide angiography. 818 87

A case of muscular dystrophy in a 1-year-old male castrated Domestic Shorthair cat is presented. The most striking clinical features were regurgitation, a stiff gait, an increased muscle tone and exercise intolerance. Serum biochemistry panels showed a marked increase in the muscle specific enzyme creatine kinase, and moderately elevated levels of LDH, AST and ALT. Spontaneous electrical activity of skeletal muscles in the form of "bizarre high frequency discharges" and "myotonia-like repetitive discharges" were registered. Gross pathology revealed a marked hypertrophy of the skeletal muscles. The main histopathological changes were myofiber necrosis and calcification, variation in fiber size, hypertrophied muscle fibers of type I and type II and fiber splitting. Indirect immunofluorescence showed dystrophin deficiency. Feline muscular dystrophy resembles the X-linked human Duchenne muscular dystrophy (DMD). Besides the X-linked muscular dystrophy in the mouse and Golden Retriever the feline muscular dystrophy could represent another valuable animal model for the study of DMD.
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PMID:[Muscular dystrophy in a cat]. 824 6

Duchene muscular dystrophy (DMD) is a fatal progressive X-linked muscle disorder, caused by mutations in the dystrophin gene. We have investigated adenovirus-mediated transfer of a dystrophin minigene in a mutant mouse lacking dystrophin, the mdx mouse. We report here that six months after a single intramuscular injection of a recombinant adenovirus containing a human dystrophin minigene, a large number of dystrophin-positive fibres are still detected in the injected muscles. Moreover, although the minigene encodes a truncated protein, its expression is able to protect the fibres efficiently against the degeneration process that affects the dystrophin-deficient mdx myofibres.
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PMID:Long-term correction of mouse dystrophic degeneration by adenovirus-mediated transfer of a minidystrophin gene. 825 38

Duchenne progressive muscular dystrophy is a lethal and common X-linked genetic disease caused by the absence of dystrophin, a 427K protein encoded by a 14 kilobase transcript. Two approaches have been proposed to correct the dystrophin deficiency in muscle. The first, myoblast transfer therapy, uses cells from normal donors, whereas the second involves direct intramuscular injection of recombinant plasmids expressing dystrophin. Adenovirus is an efficient vector for in vivo expression of various foreign genes. It has recently been demonstrated that a recombinant adenovirus expressing the lac-Z reporter gene can infect stably many mouse tissues, particularly muscle and heart. We have tested the ability of a recombinant adenovirus, containing a 6.3 kilobase pair Becker-like dystrophin complementary DNA driven by the Rous sarcoma virus promoter to direct the expression of a 'minidystrophin' in infected 293 cells and C2 myoblasts, and in the mdx mouse, after intramuscular injection. We report here that in vivo, we have obtained a sarcolemmal immunostaining in up to 50% of fibres of the injected muscle.
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PMID:Efficient adenovirus-mediated transfer of a human minidystrophin gene to skeletal muscle of mdx mice. 843 25

Identification of the defective gene and the absent gene product dystrophin can substantiate the clinical evidence for manifesting X-linked Duchenne type muscular dystrophy (DMD). It is not always possible, however, to rule out definitely a clinically asymptomatic carrier status in question, since even in the proven carrier DNA analysis is often inconclusive, and multinucleated skeletal muscle fibers express a basically normal membrane dystrophin. To substantiate the value of endomyocardial biopsy as a new tool for detection of the DMD carrier status we examined an endomyocardial biopsy of a volunteer who met the clinical criteria of a DMD carrier. Dystrophin immunohistochemistry and western blot of her skeletal muscle biopsy were inconclusive, and polymerase chain reaction and cDNA analysis failed to locate directly the X-chromosomal defect. We observed a clearcut mosaic of dystrophin-positive and -negative mononucleated cardiac muscle cells, reflecting a heterozygote carrier status in her endomyocardial biopsy, whereas 20 controls were uniformely positive. The incidence of DMD (1:3000 males) and especially the 30% spontaneous mutation rate, still the major pitfall in DNA analysis, show the need for an additional diagnostic tool.
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PMID:Heterozygotic gene expression in endomyocardial biopsies: a new diagnostic tool confirms the Duchenne carrier status. 848 29


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