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)

Congenital adrenal hypoplasia (CAH) normally occurs in the neonatal period, with patients presenting with more or less severe salt-wasting syndrome. X-linked CAH has been associated with mutations in the DAX-1 gene, and boys have also been shown to have hypogonadotrophic hypogonadism. Recently, in three unrelated boys, CAH was associated with intrauterine growth retardation (IUGR), metaphyseal dysplasia and genital abnormalities, defining a new association called IMAGe. We now report four additional patients with this association, including the first living female. The four patients belong to two unrelated families (one brother and one sister from each family). These patients have the main clinical characteristics of IMAGe association: IUGR, facial dysmorphy (frontal bossing, broad nasal bridge, low-set ears), short limbs due to metaphyseal dysplasia, and adrenal insufficiency. As these patients are older than the initial three patients, we can also describe additional features: short adult height, normal puberty in boys as well as in the living girl. The boys have hypospadias associated with micropenis. The living girl came to clinical attention at the age of 5 years as a result of a familial survey, and careful questioning revealed that she had been suffering from mild adrenal insufficiency since early childhood. At least one boy has congenital hypotonia due to muscular dystrophy. In conclusion, these four new cases display familial transmission, strongly suggesting Mendelian autosomal recessive inheritance. Adrenal insufficiency may be mild. Hypotonia, described in all the patients, might be related to paucisymptomatic muscular dystrophy, as this condition is clearly heterogeneous varying with regard to severity, associated manifestations and outcome. If this symptom is part of the syndrome, which we cannot assume, it could help to localize the candidate gene.
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PMID:IMAGe association: additional clinical features and evidence for recessive autosomal inheritance. 1206 32

There is a pressing need to develop new therapeutic approaches to Duchenne muscular dystrophy, an X-linked fatal disease primarily affecting skeletal and cardiac muscle. Gene therapy is an approach that has attracted much interest since the description of the Duchenne muscular dystrophy gene and its mutations in 1987. Since 1990 numerous reporter and dystrophin gene transfer studies have been conducted on muscles of animals but mostly in mice. Experimental protocols have ranged from germ-line gene transfer (via the production of transgenics) to somatic gene transfer studies using viral or non-viral vectors. But what have we actually learned from such studies that can be applied to patients with Duchenne muscular dystrophy? Various dystrophin, utrophin and integrin recombinant cDNAs have been shown to prevent the development of muscular dystrophy in transgenic dystrophic (mdx) mice. Somatic gene transfer prior to the onset of pathology have been shown to prevent the development of the muscular dystrophy in the mdx mouse but the data is less convincing for the beneficial effects of somatic gene transfer following the establishment of pathology. The time of onset and the course of the disease differ substantially between mouse and man and raise concerns about the applicability of gene therapy in man where the disease manifests in utero and the progression is more severe. The other major concern relates to uncertainty over the efficiency of the different vectors in man, particularly as many patients are likely to have encountered the infectious forms of the viruses that are proposed as vectors.
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PMID:Gene transfer studies in animals: what do they really tell us about the prospects for gene therapy in DMD? 1220 90

Cardiopathy is an expected finding in X-linked Duchenne and Becker muscular dystrophies. This holds true for some other forms such as autosomal recessive limb-girdle dystrophies. However, data on early-onset and usually severe congenital muscular dystrophies are limited. The purpose of this study was to investigate the presence of cardiac involvement in children with merosin-positive congenital muscular dystrophy. A total of 42 patients and 22 healthy subjects were evaluated by M-mode, 2D, and Doppler echocardiography. Cardiac anatomy, left ventricular dimensions, wall thickness and systolic and diastolic functions were investigated in patients and compared with those of healthy control subjects. Mean left ventricular ejection fraction and shortening fraction were significantly lower in the patient group (P<0.05 and P<0.001, respectively) and in three patients ejection fraction was below 55%. Although some impairments in left ventricular inflow indexes which were suggestive of left ventricular diastolic dysfunction were detected in patients with merosin-positive congenital muscular dystrophy they were not statistically significant. Our results suggest that left ventricular systolic abnormalities may occur in children with merosin-positive congenital muscular dystrophy.
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PMID:Assessment of left ventricular systolic and diastolic functions in children with merosin-positive congenital muscular dystrophy. 1255 29

The experience of DNA-diagnosis of X-linked recessive Emery-Dreifuss muscular dystrophy for the first time made in Russia is presented. A search for mutations in emerin gene responsible for the disease has been conducted in 13 blood samples of male patients with clinical diagnosis of various muscular dystrophy. Mutations were found in 2 patients. In one of them clinical diagnosis of Emery-Dreifuss muscular dystrophy was confirmed. In the other, a novel mutation was described that allowed to change a clinical diagnosis of limb girdle muscular dystrophy. X-linked and clinically identical autosomal-dominant forms of Emery-Dreifuss muscular dystrophy are characterized by pronounced clinical polymorphism complicating clinical diagnosis. DNA-diagnosis principally extends possibilities for early diagnosis of this disorder that is extremely important for prevention of severe and frequently lethal heart diseases.
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PMID:[DNA-diagnosis of Emery-Dreifuss muscular dystrophy]. 1287 22

Spinal deformity in the form of kyphosis or kyphoscoliosis occurs in most patients with Duchenne muscular dystrophy (DMD), a fatal X-linked disorder caused by an absence of the subsarcolemmal protein dystrophin. Mdx mice, which also lack dystrophin, show thoracolumbar kyphosis that progresses with age. We hypothesize that paraspinal and respiratory muscle weakness and fibrosis are associated with the progression of spinal deformity in this mouse model, and similar to DMD patients there is evidence of altered thoracic conformation and area. We measured kyphosis in mdx and age-matched control mice by monthly radiographs and the application of a novel radiographic index, the kyphotic index, similar to that used in boys with DMD. Kyphotic index became significantly less in mdx at 9 mo of age (3.58 +/- 0.12 compared with 4.27 +/- 0.04 in the control strain; P < or = 0.01), indicating more severe kyphosis, and remained less from 10 to 17 mo of age. Thoracic area in 17-mo-old mdx was reduced by 14% compared with control mice (P < or = 0.05). Peak tetanic tension was significantly lower in mdx and fell 47% in old mdx latissimus dorsi muscles, 44% in intercostal strips, and 73% in diaphragm strips (P < or = 0.05). Fibrosis of these muscles and the longissimus dorsi, measured by hydroxyproline analysis and histological grading of picrosirius red-stained sections, was greater in mdx (P < 0.05). We conclude that kyphotic index is a useful measure in mdx and other kyphotic mouse strains, and assessment of paralumbar and accessory respiratory muscles enhance understanding of spinal deformity in muscular dystrophy.
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PMID:Progression of kyphosis in mdx mice. 1523 60

The review summarizes the results of a decade of molecular genetic studies of several high-incidence hereditary neurodegenerative diseases, including primary parkinsonism, various forms of hereditary dystonia and ataxia, polyglutamine disorders, hepatolenticular degeneration, essential tremor, etc. Various relevant mutations were studied. The character and frequencies of particular mutations and the corresponding genetic disorders were established for the Russian population. Particular genotypes were associated with various clinical variants of the diseases. Genetic loci were identified for several unique hereditary diseases of the nervous system (X-linked cerebellar hypoplasia, an atypical form of autosomal recessive muscular dystrophy, etc.). Nosological positions of the relevant clinical forms were clarified on the basis of the molecular genetic data. Protocols were developed for direct or indirect DNA diagnostics of the diseases under study to improve medical genetic counseling and prevention of new disease cases in affected families.
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PMID:[Molecular genetic analysis of hereditary neurodegenerative diseases]. 1534 Dec 72

The Arabs in general are genetically diverse. Major factors that contributed to their diversity include the migrations of Semitic tribes from the Arabian Peninsula, the Islamic expansion in the 7th century AD, the Crusade wars and the recent migration dynamics. These events have resulted in the admixture of the original Arabs with other populations extending from east and south Asia to Europe and Africa. Their demographic features include high rates of consanguinity, a large family size and a rapid population growth. There is a high frequency of autosomal recessive disorders and increased frequencies of homozygosity for autosomal dominant traits, such as familial hypercholesterolemia and X-linked traits, such as glucose-6-phosphate dehydrogenase deficiency. The patterns of autosomal recessive disorders, including their mutations, may be different in various geographic locations within the Arab world. However, there are disorders that are specifically prevalent among the Arabs either uniformly or in certain locations. The Arab Genetic diseases include Bardet-Biedl syndrome, Meckel syndrome, autosomal recessive severe childhood muscular dystrophy, osteopetrosis and renal tubular acidosis, Sanjad-Sakati syndrome and others.
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PMID:Genetic diversity among the Arabs. 1576 50

We systematically screened the whole coding region of 18 male muscular dystrophy patients whose clinical, histological and laboratory findings suggest Becker muscular dystrophy (present but abnormal dystrophin). No systematic mutation study of a cohort of patients with dystrophin of normal quality but abnormal quantity has been published. The complete coding sequence of the dystrophin gene (11 kb) of each patient was subjected to an automated sequence analysis by using muscle biopsy RNA; 535 bp of the gene promoter and 5'UTR were likewise sequenced. We identified seven disease-causing mutations (40%). Six were novel, including missense, nonsense, small deletion and splice site mutations. Sixty percent (11/18) of patients with decreased quantities of normal molecular weight dystrophin showed no mutation, but most of them had a family history highly suggestive of X-linked inheritance, suggesting transcription or translational deleterious affection, i.e. outside what was screened. Quantitative multiplex fluorescence polymerase chain studies of mutation-negative patients showed normal levels of dystrophin mRNA. In three patients, there was some reduction of the transcript suggesting a deleterious undetected gene change resulted in the reduction of RNA levels. Our data address important structure/function and genotype/phenotype correlations and it suggests that dystrophin protein studies must be interpreted with caution in deletion-negative male muscular dystrophy patients.
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PMID:DNA sequence analysis for structure/function and mutation studies in Becker muscular dystrophy. 1595 89

Mutations within LMNA, encoding A-type nuclear lamins, are associated with multiple tissue-specific diseases, including Emery-Dreifuss (EDMD2/3) and Limb-Girdle muscular dystrophy (LGMD1B). X-linked EDMD results from mutations in emerin, a lamin A-associated protein. The mechanisms through which these mutations cause muscular dystrophy are not understood. Here we show that most, but not all, cultured muscle cells from lamin A/C knockout mice exhibit impaired differentiation kinetics and reduced differentiation potential. Similarly, normal muscle cells that have been RNA interference (RNAi) down-regulated for either A-type lamins or emerin have impaired differentiation potentials. Replicative myoblasts lacking A-type lamins or emerin also have decreased levels of proteins important for muscle differentiation including pRB, MyoD, desmin, and M-cadherin; up-regulated Myf5; but no changes in Pax3, Pax7, MEF2C, MEF2D, c-met, and beta-catenin. To determine whether impaired myogenesis is linked to reduced MyoD or desmin levels, these proteins were individually expressed in Lmna(-/-) myoblasts that were then induced to undergo myogenesis. Expression of either MyoD or, more surprisingly, desmin in Lmna(-/-) myoblasts resulted in increased differentiation potential. These studies indicate roles for A-type lamins and emerin in myogenic differentiation and also suggest that these effects are at least in part due to decreased endogenous levels of other critical myoblast proteins. The delayed differentiation kinetics and decreased differentiation potential of lamin A/C-deficient and emerin-deficient myoblasts may in part underlie the dystrophic phenotypes observed in patients with EDMD.
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PMID:Lamin A/C and emerin are critical for skeletal muscle satellite cell differentiation. 1648 76

The Emery-Dreifuss muscular dystrophy is a form of muscular dystrophy that frequently presents early contractures and cardiac conduction defects, caused by emerin deficiency in the inner nuclear membrane of the muscular fibers. A 19-years-old man it presented muscle weakness and hypotrophy in the proximal upper and lower limbs, dysphagia and early contractures in elbows and ankles, with familiar history compatible with X-linked inheritance form. The investigation showed increased serum creatinekinase levels electrocardiogram had a first degree atrioventricular block and right bundle branch block normal electromyography and nerve conduction study muscle biopsy disclosed myopathic characteristics and nuclear protein immunohystochemical analysis showed deficiency of emerin. The clinical and genetics manifestations, laboratorial and electromyography changes, as well as, the study of the pattern of inheritance for genetic counseling are discussed.
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PMID:[Emery-Dreifuss muscular dystrophy: case report]. 1679 77


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