Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Duchenne and Becker muscular dystrophies (DMD and BMD) are two allelic recessive X-linked disorders. Molecular deletions of various regions of the dystrophin gene are the main mutations detected in DMD and BMD patients. Molecular study of DMD and BMD DNA are instrumental to understand the pathological molecular mechanisms and the function of the protein. We describe here dystrophin and its interaction with a glycoprotein complex and we then focus on two particular patients with partial deletions of the dystrophin gene: 1) a typical Becker patient, who shows an intragenic deletion disrupting the reading frame. We describe in this case alternative splicings restoring the reading frame, which might explain the mild clinical phenotype of this patient, 2) a deletion of the distal part of the DMD gene coding for the carboxyterminal domain of the dystrophin in a young patient. The normal localization of dystrophin at the inner face of the plasma membrane in the muscle of this patient suggests that the last domain of this protein is not sufficient to anchor dystrophin at the membrane.
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PMID:[Molecular pathology of Duchenne and Becker muscular dystrophy]. 130 Dec 22

The differential clinical diagnosis between the X-linked muscular dystrophies (DMD and BMD) and autosomal recessive limb-girdle muscular dystrophy (LGMD), which is extremely important for genetic counseling, may be very difficult. The aim of the present report is to describe clinical and laboratory findings in patients from large families, with AR inheritance, in an attempt to characterize better cases which have been diagnosed as LGMD compared with the X-linked forms. The main features analysed are: age of onset and of confinement to a wheelchair, reproductive performance, serum enzymes (CK and PK) and dystrophin assessment (through immunohistochemistry and Western blot). Twenty-two families, with 62 affected patients diagnosed as limb-girdle muscular dystrophy, were included in this report. In 19 families, the patients had a milder clinical course, while in the remaining 3, the progression of the disease was continuous and clinically similar to X-linked DMD ("DMD-like"). A high consanguinity rate was observed among the parents of the affected patients (77%). No major clinical difference was observed between the X-linked and the AR forms. However, muscle dystrophin was found qualitatively and quantitatively normal in the autosomal forms but absent or abnormal in the X-linked ones. The reproductive performance was significantly higher for male than female patients. In addition, a surprising finding was the significantly greater fitness estimated for male LGMD cases as compared with Becker patients of comparable age studied in our center. The implications of such findings are discussed.
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PMID:Limb-girdle syndrome: a genetic study of 22 large Brazilian families. Comparison with X-linked Duchenne and Becker dystrophies. 186 35

DMD and BMD are now understood at the genetic, biochemical, and molecular levels. At the genetic level, both disorders result from mutations of the X-linked gene encoding dystrophin. At the biochemical level, DMD results from the deficiency of a large protein called dystrophin, whereas BMD results when dystrophin is present, though abnormal in either amount or molecular structure. To date, thousands of patients have been analyzed for mutations of the dystrophin gene in peripheral blood DNA or alterations of the dystrophin protein in muscle tissue. The severity of the clinical phenotype of these patients has been compared with their dystrophin gene mutations and corresponding dystrophin protein alterations, revealing an unexpectedly high degree of correlation. Thus, information derived from the molecular analysis (DNA or protein) of a particular patient provides a "molecular diagnosis," which is highly predictive of the clinical course that patient can be expected to follow. Because molecular diagnoses are independent of the patient's age, they provide a prognosis for the large majority of muscular dystrophy patients even before clinical symptoms of their disease become apparent. Such prognostic molecular diagnoses have proven particularly valuable when the patient is an isolated case, with no family history for the disorder. Prenatal genetic diagnosis of DMD or BMD may involve use of Southern blot or PCR techniques to search for a deletion in the DNA of at-risk fetuses or more complicated family linkage studies using intragenic and flanking RFLPs. More recently, assay of dystrophin content in fetal skeletal or cardiac muscle from at-risk abortuses has been accomplished, allowing definitive discrimination of affected and normal fetuses in cases in which deletion analyses and family DNA studies were equivocal. In utero fetal skeletal muscle biopsy for dystrophin protein assay has actually been accomplished in at least one at-risk pregnancy in which family DNA studies were uninformative. Dystrophin was present in skeletal muscle from this 20-week-old male fetus, and the pregnancy continued, resulting in the term birth of a healthy male infant. The future holds exciting opportunities for neonatal screening and treatment of these devastating neuromuscular diseases.
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PMID:Duchenne and Becker muscular dystrophies: genetics, prenatal diagnosis, and future prospects. 228 31

The distribution of HLA class I and class II antigens has been investigated in cryostat sections of a series of 200 skeletal muscle biopsy specimens from patients with various neuromuscular disorders. Normal muscle fibres expressed no detectable class I antigens, whereas muscle fibres of patients with inflammatory myopathies and Duchenne (DMD) and Becker (BMD) muscular dystrophy showed consistently strong expression. In other neuromuscular diseases expression of class I antigens was more variable. No expression of class I antigens was observed on muscle fibres in samples from fetuses "at risk" for DMD and BMD or from female carriers of these disorders. The immunocytochemical assessment of HLA class I antigen expression was confirmed by a quantitative radioimmunoassay which demonstrated a 3-fold increase in the level of expression in muscle samples from patients with DMD and juvenile dermatomyositis. Class II antigen expression was never observed on muscle fibres in biopsies from normal individuals or any of the neuromuscular disorders. However, these antigens were expressed by endothelial cells present in these samples. Muscle specimens from fetuses and early in postnatal life showed very limited expression of class II antigens. They were expressed at a reduced level by about 3 months of age, but strong expression of class II antigens was not observed until about 1 year of age. The mechanism of induction of class I antigen expression in diseased muscle is not known. The appearance of class I antigens on diseased muscle may make the affected tissue a target for cytotoxic T cells and may thus have a role in muscle fibre damage in inflammatory myopathies and the X-linked muscular dystrophies.
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PMID:Expression of class I and class II MHC antigens in neuromuscular diseases. 292 49

A series of 95 families, consisting of 317 patients with severe and mild X-linked proximal pseudohypertrophic muscular dystrophy (MD), was analysed by the use of two different and rigid clinical criteria based on the age when the patient became chairbound. Using these criteria the families from Erfurt and Warsaw could be clearly separated into classical Duchenne (DMD) and classical Becker (BMD) type patients. A third group of patients was found with atypical clinical course, who could not be identified as neither Duchenne nor Becker cases. Statistically highly significant differences were found between the groups of classical DMD and atypical MD cases on the one hand and between the groups of atypical MD and classical BMD cases on the other, especially with respect to age when chairbound and age at death. The comparisons of progression of the disease, life expectancy and of fertility between the three groups of X-linked MD show that classical DMD and atypical MD may be considered as separate types of severe X-linked proximal pseudohypertrophic MD. On the basis of these findings the authors offer conclusions for the general practice of neurology, paediatrics and genetic counseling.
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PMID:Atypical form of X-linked proximal pseudohypertrophic muscular dystrophy. 358 25

Determination of serum creatine phosphokinase (CPK) activity is often used in efforts to detect carriers of X-linked muscular dystrophies. We have recently demonstrated that another serum enzyme, pyruvate-kinase (PK) may also be of use in the diagnosis of patients affected with a variety of neuromuscular disorders. To evaluate the usefulness of this assay for carrier detection, a comparative study of serum PK and CPK activity was performed in 74 female relatives of patients affected with Duchenne (DMD) and Becker (BMD) muscular dystrophies. For obligate carriers of the DMD gene, 10 of 14 had elevated CPK's, 11 of 14 had elevated PK's and 12 of 14 had abnormal results for either of the two enzymes. Three of 16 mothers of isolated cases had increased serum CPK activity and 6 of 16 had increased PK activity (7 had elevation of at least one enzyme). These preliminary data suggest that the use of PK may enhance the capability to discriminate carriers for these X-linked recessive genes.
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PMID:Serum pyruvate-kinase (PK) and creatine-phosphokinase (CPK) in female relatives and patients with X-linked muscular dystrophies (Duchenne and Becker). 738 16

Duchenne and Becker muscular dystrophy (DMD/BMD) are recessive X-linked neuromuscular diseases produced by allelic mutations in the human dystrophin gen. In the present study we determined the 14-deletion prone exons by multiplex PCR in 24 no related venezuelan patients with clinical diagnosis of DMD/BMD. We found 37% of intragenic deletions of which 77% were located at the "hot spot" deletion region that includes exons 44 to 55. The present study show that deletion frequency observed in venezuelan patients resembles some Asian populations and is lower than that observed in Europe and North America. The explanation of the low frequency detected in our patients is beyond the present study, but it is likely that different mutations, ocurring at other regions of the gene is determining a molecular heterogeneity of the DMD/BMD disease in Venezuela.
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PMID:[Molecular diagnosis of Duchenne/Becker muscular dystrophy in Venezuelan patients with the polymerase chain reaction]. 773 22

A neurologically asymptomatic 32-yr-old man recently transplanted for end-stage dilated cardiomyopathy presented with progressively increasing serum creatine kinase level (hyperCKemia) while receiving cyclosporin and simvastatine treatment. Revised family history led to suspicion of X-linked inherited myopathy, then confirmed by muscle biopsy findings showing myopathic dystrophic changes, a patchy distribution of immunoreactivity on the sarcolemma of several muscle fibres with anti-dystrophin antibodies and a double dystrophin band of normal and lower molecular weight on immunoblot analysis. A molecular genetic study demonstrated a deletion spanning over exons 45-47 at Xp21 locus. Routine neurological evaluation and currently available laboratory investigation may lead to early diagnosis of otherwise unrecognized Xp21 BMD among patients presenting with dilated cardiomyopathy alone, thus avoiding subsequent diagnostic difficulties.
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PMID:Dilated cardiomyopathy requiring cardiac transplantation as initial manifestation of Xp21 Becker type muscular dystrophy. 801 95

Duchenne and Becker muscular dystrophies (DMD and BMD) are allelic X-linked disorders arising from mutations in the (2.4 Mb) dystrophin gene at Xp21. We have applied the reverse transcriptase-polymerase chain reaction (RT-PCR) to identify a larger than normal dystrophin mRNA from a male with Duchenne muscular dystrophy and his younger affected brother. The increased size of the dystrophin mRNA was due to a splice-site mutation at the exon 26:intron 26 junction where a T to G substitution prevented normal RNA processing. A cryptic splice-site, downstream of the mutation, was activated during processing, resulting in the inclusion of 117 bases of intron 26. This insertion introduced an in-frame stop codon into the mature dystrophin mRNA. An allele-specific test was developed to identify the mutation and was applied to this family. Interestingly, the mother of the two affected boys did not carry the mutation, as determined by allele-specific amplification and direct DNA sequence analysis, indicating gonadal mosaicism. Her eldest daughter, designated as a carrier based upon conventional testing and haplotype analysis, also did not carry the family mutation. Initial haplotyping of the family appeared to be straightforward with gonadal mosaicism becoming evident only after allele-specific analysis. The application of linked markers to identify the disease allele for conventional genetic counselling would have been erroneous in this family and highlights the diagnostic power of precise identification of the disease-causing mutation.
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PMID:Identification of a point mutation and germinal mosaicism in a Duchenne muscular dystrophy family. 819 94

We have analysed the results of clinical assessment, X-inactivation status, deletion screening and dystrophin analysis in eight manifesting carriers of Duchenne and Becker muscular dystrophy (DMD and BMD). Only two had a prior family history of X-linked muscle disease, all had normal karyotypes and none were twins. Presentation varied from 2 to 25 yr and progression varied from a DMD-like severity to a very mild BMD-like course. In one girl the initial symptoms were restricted to learning difficulties. Where methods for assessing X-inactivation were informative, three patients showed an abnormal pattern. However, in one patient, the obligate carrier daughter of a BMD patient who had presented at the age of 2 yr, X-inactivation appeared normal in lymphocytes and muscle. While dystrophin analysis seems to be reliable in identifying manifesting carriers of DMD and BMD, the relationship between X-inactivation status, dystrophin analysis and phenotype is not simple.
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PMID:Variability in clinical, genetic and protein abnormalities in manifesting carriers of Duchenne and Becker muscular dystrophy. 832 90


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