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

Congenital malformations and inherited disorders constitute a substantial proportion of the afflictions seen in sheep and goats. Of these, malformations tend to be similar in both species, whereas the genetic diseases encountered to date, with the exception of a few, are different. Of the 28 genetic diseases of sheep and goats described in this review, 60% and 62.5%, respectively, are monogenic disorders. For a majority of the monogenic recessive disorders encountered in these species, the carrier state is not detectable at present, whereas in others, in which a biochemical lesion is known (dermatosparaxis, erythrocyte glutathione deficiency, globoid cell leukodystrophy and glycogen storage disease), the carrier state is detectable with the aid of enzyme and surface protein markers. The latter group and the dominant disorders (anury, cataract, glomerulonephritis, and lethal grey in sheep; gynecomastia and anotia-microtia complex in goats) are easy to eliminate through selective breeding. The polygenic disorders (entropion, epidermolysis bullosa, hereditary chondrodysplasia, and muscular dystrophy of sheep, and udder problems in goats) are more difficult to eradicate, because the mutant genes responsible for these traits generally do not declare themselves until inbreeding brings together a critical concentration to create a health crisis in some, whereas others, which are only short of a few of these mutant genes, might go totally unaffected and therefore undetected. Chromosome defects of the structural nature (translocations) seen in sheep and goats generally create meiotic disturbances, which in a majority of cases lead to subfertility, whereas sex chromosome aneuploids are generally sterile.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Genetic diseases of sheep and goats. 224 74

With few exceptions, epidermolysis bullosa (EB) simplex is an autosomal dominant disorder characterized by rather localized and recurrent nonscarring blister formation; mucous membranes and other organs are usually uninvolved. Recently, two patients were described with an autosomal recessive form of EB simplex associated with muscular dystrophy. We now describe four additional patients with autosomal recessive EB simplex, three of whom had associated muscular dystrophy or congenital myasthenia gravis. These patients had generalized cutaneous findings, including milia, atrophic scarring, nail dystrophy, and scalp alopecia, which have been classically attributed to either junctional or dystrophic EB. Each patient had significant oral cavity involvement, and in two, marked growth retardation and anemia were also present. Our findings suggest that autosomal recessive EB simplex may be characterized by rather severe cutaneous and extracutaneous disease activity, and may be associated with at least two distinct neuromuscular diseases.
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PMID:Autosomal recessive epidermolysis bullosa simplex. Generalized phenotypic features suggestive of junctional or dystrophic epidermolysis bullosa, and association with neuromuscular diseases. 266 9

Epidermolysis bullosa with unusually severe clinical features was associated with progressive muscular dystrophy in two siblings. Light and electron microscopic examination revealed an intraepidermal cleavage confirming that this mechanobullous disease belonged to the epidermolysis bullosa simplex group. This may represent a new disease entity inherited in an autosomal-recessive fashion.
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PMID:Epidermolysis bullosa simplex associated with muscular dystrophy with recessive inheritance. 335 99

Phenytoin has a wide range of pharmacologic effects other than its anticonvulsant activity. It has been the subject of more than 8,000 published papers, which include clinical reports of its usefulness in approximately 100 diseases and symptoms. In the United States the only indications for use in the official labeling for phenytoin are various types of seizures. An advisory committee of the Food and Drug Administration recently recommended the addition of certain cardiac arrhythmias to the labeling. To determine whether other uses should be added to the labeling and whether additional clinical trials should be encouraged, an in-depth review of the published literature was undertaken. This review revealed that, on the basis of controlled studies, phenytoin is probably useful in the continuous muscle fiber activity syndrome, myotonic muscular dystrophy, and myotonia congenita. In addition, phenytoin appears to be potentially useful in recessive dystrophic epidermolysis bullosa, intermittent explosive disorder, anxiety disorder in which anger and irritability are prominent features, and, topically, in burns and refractory skin ulcers. Additional clinical studies are needed before definitive conclusions can be drawn. Clinical trials of phenytoin in most of these disorders are ongoing or are contemplated. Any labeling changes will await results of the studies. Based on phenytoin's pharmacologic effects in animals, controlled trials of the drug appear to be warranted in cerebral ischemia and stroke, spinal cord injury, angina pectoris, and fractures in which the rate of healing is poor.
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PMID:Phenytoin revisited. 638 10

We report an infant with a rare form of epidermolysis bullosa simplex characterized by an autosomal recessive pattern of inheritance, severe cutaneous involvement, oral and nail lesions, associated with muscular dystrophy, and a poor prognosis, due to extracutaneous disease. In addition to the usual presentation of this disease, our patient had severe anemia, with immature circulating white cells, and bone marrow histology suggestive of a pre-leukemic state, a finding which has not before been reported in the literature.
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PMID:Epidermolysis bullosa simplex associated with muscular dystrophy: a new case. 789 87

A 20-year-old patient was born with epidermolysis bullosa and a severe, slowly progressive muscle disease. Skin biopsy demonstrated junctional epidermolysis bullosa. Muscle biopsy demonstrated degenerative changes with increase in connective tissue, fibre size variability, rods and cytoplasmic bodies, central nuclei. In muscle biopsy dystrophin, chondroitin unsulphate, chondroitin 4-sulphate, chondroitin 6-sulphate, heparan sulphate, collagen III, collagen IV and VI, laminin, and fibronectin were normally distributed. This is the first report of the association of a form of congenital muscular dystrophy with junctional epidermolysis bullosa and, together with the previous reports of muscle involvement in epidermolysis bullosa simplex and dystrophica, it suggests the existence of a syndrome characterized by the contemporaneous presence of skin and muscle involvement.
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PMID:Congenital muscular dystrophy associated with familial junctional epidermolysis bullosa letalis. 830 68

We report that mutation in the gene for plectin, a cytoskeleton-membrane anchorage protein, is a cause of autosomal recessive muscular dystrophy associated with skin blistering (epidermolysis bullosa simplex). The evidence comes from absence of plectin by antibody staining in affected individuals from four families, supportive genetic analysis (localization of the human plectin gene to chromosome 8q24.13-qter and evidence for disease segregation with markers in this region) and finally the identification of a homozygous frameshift mutation detected in plectin cDNA. Absence of the large multifunctional cytoskeleton protein plectin can simultaneously account for structural failure in both muscle and skin.
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PMID:Plectin deficiency results in muscular dystrophy with epidermolysis bullosa. 869 40

Plectin is a widely expressed high molecular weight protein that is involved in cytoskeleton-membrane attachment in epithelial cells, muscle, and other tissues. The human autosomal recessive disorder epidermolysis bullosa with muscular dystrophy (MD-EBS) shows epidermal blister formation at the level of the hemidesmosome and is associated with a myopathy of unknown etiology. Here, plectin was found to be absent in skin and cultured keratinocytes from an MD-EBS patient by immunofluorescence and immunoprecipitation, suggesting that plectin is a candidate gene/protein system for MD-EBS mutation. The 14800-bp human plectin cDNA was cloned and sequenced. The predicted 518-kD polypeptide has homology to the actin-binding domain of the dystrophin family at the amino terminus, a central rod domain, and homology to the intermediate filament-associated protein desmoplakin at the carboxyl terminus. The corresponding human gene (PLEC1), consisting of 33 exons spanning >26 kb of genomic DNA was cloned, sequenced, and mapped to chromosomal band 8q24. Homozygosity by descent was observed in the consanguineous MD-EBS family with intragenic plectin polymorphisms. Direct sequencing of PCR-amplified plectin cDNA from the patient's keratinocytes revealed a homozygous 8-bp deletion in exon 32 causing a frameshift and a premature termination codon 42 bp downstream. The clinically unaffected parents of the proband were found to be heterozygous carriers of the mutation. These results establish the molecular basis of MD-EBS in this family and clearly demonstrate the important structural role for plectin in cytoskeleton-membrane adherence in both skin and muscle.
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PMID:Loss of plectin causes epidermolysis bullosa with muscular dystrophy: cDNA cloning and genomic organization. 869 33

In a distinct autosomal recessive variant of epidermolysis bullosa, EB-MD, life-long skin blistering is associated with late-onset muscular dystrophy of unknown etiology. Electron microscopy of these patients' skin suggests that tissue separation occurs intracellularly at the level of the hemidesmosomal inner plaque, which contains plectin, a high molecular weight cytoskeletal associated protein, also expressed in the sarcolemma of the muscle. In this study, we report two patients with EB-MD, each with a homozygous deletion mutation in the plectin gene, PLEC1. In the first case, the proband and her similarly affected sister had a homozygous 9 bp deletion mutation, designated as 2719de19, which resulted in elimination of three amino acids, QEA, in a sequence of 23 amino acids entirely conserved between the mouse and human sequences. The proband in the second family demonstrated a single nucleotide deletion at position 5866, designated as 5866delC, which resulted in frameshift and a premature termination codon for translation 16 bp downstream from the site of deletion. The absence of plectin in the hemidesmosomes, as reflected by negative immunofluorescence with an anti-plectin antibody (HD-1), associated with fragility of basal keratinocytes, implicates plectin as critical for binding of intermediate keratin filament network to hemidesmosomal complexes. The function of plectin as a putative attachment protein also in the muscle would explain the clinical phenotype consisting of cutaneous fragility and muscular dystrophy in EB-MD.
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PMID:Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy. 889 87

Plectin is a widely expressed cytomatrix component involved in the attachment of the cytoskeleton to the plasma membrane. We have recently reported that the skin and muscles of three patients affected by epidermolysis bullosa simplex with muscular dystrophy (MD-EBS), a genetic disorder characterized by skin blistering associated with muscle involvement, are not reactive with antibodies specific to plectin. We demonstrated that in the skin, lack of plectin leads to failure of keratin filaments to connect to the plasma membrane via the hemidesmosomes, whereas in the muscle the deficient expression of the molecule correlates with an aberrant localization of desmin in the muscle fibers. In this study we demonstrate that in a MD-EBS kindred with two affected members, the disease results from a homozygous nonsense mutation in the plectin (PLEC1) gene leading to a premature stop codon (CGA to TGA) and decay of the aberrant plectin messenger RNA. The segregation of the mutated allele implicates the mutation in the pathology of the disorder. These results confirm the critical role of plectin in providing cell resistance to mechanical stresses both in the skin and the muscle.
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PMID:A homozygous nonsense mutation in the PLEC1 gene in patients with epidermolysis bullosa simplex with muscular dystrophy. 894 34


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