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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

X-linked DMD is a serious condition characterized by progressive muscle wasting and weakness and death ensues in the late teens or early twenties. There is considerable clinical variability even within families and some suggestions of genetic heterogeneity. Though skeletal muscle is primarily involved, other tissues are also affected including cardiac and smooth muscle. Other abnormalities include mental retardation, thymus hyperplasia and possibly certain endocrinological changes. The responsible locus is at Xp21 and the gene product is a very large protein (dystrophin) which is normally localised to muscle cell membranes. It is hypothesised that its absence in DMD may result in instability of the muscle cell membrane with resultant ingress of calcium, an increase in intracellular calcium, and cell death. An understanding of this pathway is important in devising an effective treatment.
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PMID:Clinical and molecular studies in Duchenne muscular dystrophy. 266 10

The authors emphasize the importance of adding a genetic criterion to the definition of Duchenne dystrophy. The clinical characteristics, however, on the basis of recent molecular genetic studies, are sufficiently precise to make the condition heterogeneous: two types of Duchenne dystrophy, with or without mental retardation in affected boys; muscular dystrophy in girls with mild symptomatic weakness in "manifesting carriers" up to severe myopathy in girls, found to be associated with reciprocal chromosomal translocation (X-autosome), always at the same site, Xp21. Diagnostic use of Xp21 probes is now as necessary as EMG, muscle biopsy and serum CK assay for the definition of Duchenne muscular dystrophy.
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PMID:[Present-day clinico-genetic framework of Duchenne's muscular dystrophy]. 266 13

There are some 30 or so different forms of muscular dystrophy which are conveniently classified according to the mode of inheritance. Emery-Dreifuss X-linked muscular dystrophy is characterized by the triad of: (1) early contractures of the elbows, Achilles tendons and postcervical muscles; (2) slowly progressive muscle wasting and weakness with a humero-peroneal distribution in the early stages; and (3) a cardiomyopathy usually presenting as heart-block. The insertion of a cardiac pace-maker can be life saving and therefore the recognition of the condition is essential. The responsible gene has been localized to Xq28. The autosomal recessive dystrophies are classified into congenital forms (the Fukuyama type is particularly common in Japan); a childhood form (similar to Duchenne) which occurs frequently in certain inbred communities; and adult onset limb girdle dystrophy. The autosomal dominant dystrophies are classified on the distribution of predominant muscle weakness into facioscapulohumeral, scapuloperoneal (with or without early contractures and cardiomyopathy), proximal, distal and ocular forms. The basic biochemical defects and the localizations of the responsible genes are as yet unknown in any of the autosomal recessive or autosomal dominant dystrophies.
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PMID:Emery-Dreifuss muscular dystrophy and other related disorders. 268 28

Seven unrelated women were manifesting carriers of Duchenne muscular dystrophy. A manifesting carrier of Duchenne muscular dystrophy is defined as a female with a history of Duchenne muscular dystrophy in her pedigree who has symptomatic weakness. All were characterized by slowly progressive weakness that began in the second or third decade of life. Asymmetric weakness was present in only three of the seven patients. Serum creatine kinase values were elevated in all patients and none had an electrocardiogram indicating ventricular hypertrophy. The electromyogram and muscle biopsy specimens were reported as myopathic in all patients studied. In the absence of a male relative with Duchenne muscular dystrophy, clinical distinction from cases of autosomal recessive limb girdle muscular dystrophy may not be possible. The development of new techniques in molecular genetics should allow precise identification of manifesting carriers of Duchenne muscular dystrophy in the near future.
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PMID:Duchenne muscular dystrophy manifesting carriers. 239 34

Two cases of manifesting carriers of Duchenne muscular dystrophy (DMD) were described. Case 1. The 41 year-old woman presented gait disturbance at the age of 40. She had two sons. The first son died of pneumonia soon after birth. The second son developed DMD and died of heart failure when he was 17 years old. Neurological examination revealed mild muscle weakness in neck flexors, gluteus maximus (left side dominance) and hamstrings (right side dominance) as well as bilateral calf pseudohypertrophy. Electromyography showed myopathic changes and serum creatine kinase (CK) was elevated (1941IU/l). The karyotype was 46XX. Computed tomography (CT) of skeletal muscles showed that the following muscles were partly replaced by fatty tissue: bilateral paravertebral muscles, left gluteus maximus, left quadriceps femoris, right adductor magnus, long head of right biceps femoris, bilateral peroneus longus and medial head of left gastrocnemius. Histological examination of left quadriceps femoris revealed only minimal change of focal endomysial proliferation and fiber size variation, demonstrating no necrotic fiber or no abnormalities in fiber type. Case 2. The 42 year-old woman was admitted to the hospital complaining of dyspnea and palpitation. The disease was initially diagnosed as myocardial infarction based on cardiomegaly, ECG abnormality (Q in aVL, V5,6., ST depression and negative T in V5,6, ST elevation in I, aVL) and elevated serum CK. However, the diagnosis was rejected due to the lack of subsequent changes in ECG and the continued elevation of serum CK even after her complaints had disappeared.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Asymmetrical patchy muscle involvement in manifesting carriers of Duchenne muscular dystrophy--computed tomographical and histological study]. 274 85

We studied a Becker muscular dystrophy (BMD) family with a manifesting carrier. Proximal muscle weakness, pseudohypertrophy of the calves, significantly elevated serum creatine kinase and dystrophic alterations in the muscle biopsy were the characteristic phenotypical features of this manifesting carrier. The recombinant DNA study showed a recombinant chromosome with a crossover between pERT 87-8 and pERT J-Bir in the manifesting carrier. However, the proximal part of the short arm of her X chromosome was identical to a non-manifesting carrier (her sister) and to her affected brother. For this reason, we assumed the BMD mutation was proximal to the crossover. The dystrophin cDNA probes showed no deletion of DMD/BMD gene.
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PMID:Manifesting carrier of Becker muscular dystrophy (BMD): clinical and recombinant DNA studies. 278 30

Duchenne and Becker muscular dystrophy (DMD and BMD) genes are located in Xp21 on the short arm of the X chromosome. DMD patients display a much more severe clinical course than BMD patients, and yet about 10% of cases of each have been reported to have deletions for parts of the gene. Using a complementary DNA subclone of the DMD gene we have screened 66 DMD and BMD patients who had not previously shown deletions with the probes then available. Fifteen patients have a deletion of this part of the gene, indicating a higher deletion frequency in this region (22%). Exons were deleted in five severely affected DMD patients and in ten BMD patients. Significantly, most of these deletions begin in the same region of the cDNA, which implies that there is a common mechanism for the generation of many of these mutations. An apparently identical deletion in one family gave classical BMD in two brothers (presenting in their teens) and only very mild muscle weakness in their 86-year-old great-great-uncle. Taking these data together with data using the probes previously published, we are able to detect deletions directly in 40% of our families requiring antenatal diagnosis or carrier detection.
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PMID:Preferential deletion of exons in Duchenne and Becker muscular dystrophies. 282 6

Five male Japanese patients with complex glycerol kinase deficiency (CGKD) and their relatives were studied clinically, cytogenetically, and molecular-genetically. All patients had muscular dystrophy or muscle weakness, mental retardation, congenital adrenal hypoplasia, and glycerol kinase deficiency. High-resolution GTG-banded chromosomes showed a microdeletion in the Xp21 region in all four patients examined and in all five mothers. Southern hybridizations, after digestions by restriction endonucleases, with various cloned DNAs (D2, 99-6, B24, C7, L1-4, cDMD13-14, J66-HI, P20, J-Bir, ERT87-30, ERT87-15, ERT87-8, ERT87-1, XJ-1.1, 754, cx5.7, and OTC-1) that are located around Xp21 also showed a deletion in the genome of all patients and mothers. Although the deletion differed in size among patients, a segment commonly absent was located between the genomic sequences corresponding to L1-4 and cDMD13-14. This finding indicated that the gene coding for glycerol kinase (GK) is located within this segment. A comparison of the clinical manifestations of the present five patients and reported CGKD or Duchenne muscular dystrophy (DMD) patients with DNA deletion suggests the existence of a certain gene responsible for gonadotropin deficiency (GTD). The result of the present study and results of previous studies suggest that genes for ornithine transcarbamylase (OTC), DMD, and GK and putative genes responsible for congenital adrenal hypoplasia (AHC) and GTD are arranged from telomere to centromere as pter--GTD--AHC--GK--DMD--OTC--cen.
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PMID:Complex glycerol kinase deficiency: molecular-genetic, cytogenetic, and clinical studies of five Japanese patients. 285 74

We report on two sisters with a history of muscle weakness and an electromyogram (EMG) diagnosis of Kugelberg-Welander syndrome (KWS) or juvenile spinal muscular atrophy. A half-brother to these women was diagnosed to have Duchenne muscular dystrophy (DMD). Using molecular probes, we identified a deletion within Xp21 in this isolated case of DMD. Sequences detected by pXJ1.1 are deleted, while fragments detected by pERT87 are intact. Both of these probes are derived from the DMD locus. We have shown that the affected sisters share with their half-brother DNA markers that are linked to the DMD gene and inherited from their maternal grandfather. Dosage analysis of Southern blots show monosomy for pXJ1.1, which has allowed us to determine carrier status within this family and to show that the half-sisters are manifesting DMD carriers.
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PMID:A grandpaternally derived de novo deletion within Xp21 initially presenting in carrier females diagnosed as Kugelberg-Welander syndrome. 289 84

The progression of clinical disease and serum creatine kinase (CK) levels in canine X-linked muscular dystrophy (CXMD) was studied in 7 dogs from birth to 12-14 months and in 18 dogs at varying intervals from birth to 8 weeks. One affected male was studied from age 3.5 to 6 years, and all pups were descendants of this dog. A lethal neonatal form was recognized in some pups. In the more typical form, clinical signs of stunting, weakness and gait abnormalities were evident by 6-9 weeks and were progressive, leading to marked muscle atrophy, fibrosis and contractures by 6 months. Serum CK levels were markedly elevated, such that affected pups could be identified by 1 week. CK values increased until 6-8 weeks, then plateaued at approx. 100 times normal. Affected females and beagle-cross dogs were less severely affected than large breed-cross dogs. In the 2 adult dogs with cardiac insufficiency CK levels had decreased to 5-15 times normal. These studies show that CXMD and Duchenne muscular dystrophy have striking phenotypic as well as genotypic similarities. In addition, these studies of CXMD suggest that in females and in smaller dogs the same genetic defect results in a less severe clinical disease.
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PMID:Canine X-linked muscular dystrophy. An animal model of Duchenne muscular dystrophy: clinical studies. 322 30


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