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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present a clinical and morphological study concerning a kindred with slowly progressive X-linked muscular dystrophy (Becker type). Five males were affected; one died of heart failure at age 16. Severe and early cardiac disorder is unusual in this type of muscular dystrophy, and death at such an early age had not been reported previously. In the other patients of the kindred, cardiac abnormalities, if present at all, were nonspecific. Another unusual feature in this kindred was severe muscle pain at an early stage of the disease, a feature that cannot yet be explained.
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PMID:Early myocardial disease and cramping myalgia in Becker-type muscular dystrophy: a kindred. 57

Clinical chemistry is going through an identity crisis, squeezed between automation (de-skilling) on the service side and molecular genetics in research. Automated routine estimations are now carried out and interpreted by machines; the skilled staff members required are more likely to have degrees in electronics than medicine or biochemistry. The role of molecular genetics is more ambiguous; it is inherently reductionist, in that it attempts to explain most clinical phenomena in terms of DNA sequence alone. This has been remarkably successful for single-gene defects (such as those causing Duchenne muscular dystrophy, hemoglobinopathies, cystic fibrosis, and ataxias) and may well prove equally so for Alzheimer's disease, cancer, heart disease, and schizophrenia. DNA diagnosis is not yet routine, but because of technical advances such as gene amplification ("PCR") and high-sensitivity gene-detection assays, it may soon become so, not only in major centers but also in local pathology laboratories and general practice. Clinical chemists must decide whether they wish to respond to this new and stimulating challenge by retooling and retraining. Should anyone be permitted into clinical chemistry during the 1990s without knowledge of both electronics and molecular genetics? Will there be a clinical chemistry in the twenty-first century other than through molecular genetics? This article is a personal response to these questions.
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PMID:Molecular genetics and the transformation of clinical chemistry. 233 3

Duchenne and Becker muscular dystrophy (DMD/BMD) are allelic variants caused by mutations in gene-encoding dystrophin. Abnormal expression of dystrophin in skeletal muscle has been shown to correlate with severity of disease. However, in BMD the severity of skeletal and cardiac involvement are not well correlated. We studied the immunostaining pattern of cardiac dystrophin in endomyocardial biopsy specimens from 83 patients with heart disease. Immunohistochemical assessment of dystrophin in four patients with BMD and cardiomyopathy showed a variable distributions of myocytes with continuous, discontinuous, or absent membrane immunostaining patterns. These patterns were obviously different from patterns of other heart diseases. We conclude that the discontinuous immunostaining pattern of cardiac dystrophin is characteristic of BMD and that an absent pattern may be associated with more severe cardiac dysfunction. Because genetic analysis cannot determine the correct diagnosis in 35% of DMD/BMD cases, we recommend routine examination of immunostaining patterns of dystrophin in endomyocardial biopsy specimens in patients with cardiomyopathy suspected to be the result of BMD.
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PMID:Cardiac dystrophin abnormalities in Becker muscular dystrophy assessed by endomyocardial biopsy. 790 Jun 21

A multidisciplinary study was conducted in order to assess dystrophin expression in a large series of mild X-linked muscular dystrophy patients, with well-defined clinical phenotype. Patients (104) were divided in 4 clinical groups, according to clinical severity: asymptomatic (sub-clinical), benign, moderate and severe, Cardiopathy was also assessed, and dilated cardiomyopathy was found in 47% of sub-clinical and benign cases. Myoglobinuria, cramps and myalgia were also associated with a sub-clinical or benign clinical status. Dystrophin immunohistochemical pattern of labelling and dystrophin amount decreased gradually across clinical groups. Our study showed a significative correlation between: (1) dystrophin amount and immunohistochemical score (p < 0.05); (2) dystrophin amount and clinical score (p < 0.05). Therefore, the combined use of these different techniques for prognosis of mild X-linked muscular dystrophy patients is useful. Our study assesses the prevalence of the various disease courses in a large cohort of mild X-linked muscular dystrophy patients. From our series, up to 30% of patients may be either asymptomatic or have sub-clinical changes.
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PMID:Clinical-molecular correlation in 104 mild X-linked muscular dystrophy patients: characterization of sub-clinical phenotypes. 798 92

Myocardial involvement is frequently present in Xp21-linked muscular dystrophy, due to a lack of dystrophin in cardiac fibres. We describe a 41-yr-old man affected by dilated cardiomyopathy with sporadic episodes of myoglobinuria induced by effort and increased levels of serum creatine kinase. Very mild signs of skeletal myopathy were clinically evident. His mother was affected by an indefinite cardiopathy and suddenly died when she was 36 yr old. Muscle biopsy of the patient showed a dystrophic process. Dystrophin analysis together with a genetic DMD locus study led us to diagnose Becker type muscular dystrophy, with truncated dystrophin and a gene deletion extending from exon 45 to 48. Prevalent cardiac involvement in a Becker type mutation of the dystrophin gene further confirms clinical variability of dystrophinopathies.
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PMID:Prevalent cardiac involvement in dystrophin Becker type mutation. 798 95

Endomyocardial biopsies (EMBs) of 47 patients with various cardiac disorders were analysed. Clinically 26 patients were diagnosed as having dilated cardiomyopathy (DCM), 9 myocarditis, six restrictive heart disease and six as Duchenne muscular dystrophy. EMB showed normal histological picture in six cases of DCM and findings consistent with DCM in rest of the twenty cases. None of these biopsies showed evidence of myocarditis. Diagnosis of myocarditis could be confirmed on EMB only in three out of nine clinically diagnosed cases. Cases with restrictive heart disease showed normal biopsy in two, infarction in one, findings consistent with endomyocardial fibrosis in one and amyloidosis in two cases. EMB on six cases of Duchenne muscular dystrophy showed nonspecific histological changes. To conclude, in this series, cases of DCM did not show evidence of underlying myocarditis in endomyocardial biopsies.
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PMID:Endomyocardial biopsy--its evaluation in cardiac disorders. 836 41

X-linked dilated cardiomyopathy (XLDC) is a familial heart disease presenting in young males as a rapidly progressive congestive heart failure, without clinical signs of skeletal myopathy. This condition has recently been linked to the dystrophin gene in some families and deletions encompassing the genomic region coding for the first muscle exon have been detected. In order to identify the defect responsible for this disease at the molecular level and to understand the reasons for the selective heart involvement, a family with a severe form of XLDC was studied. In the affected members, no deletions of the dystrophin gene were observed. Analysis of the muscle promoter, first exon and intron regions revealed the presence of a single point mutation at the first exon-intron boundary, inactivating the universally conserved 5' splice site consensus sequence of the first intron. This mutation introduced a new restriction site for MseI, which cosegregates with the disease in the analyzed family. Expression of the major dystrophin mRNA isoforms (from the muscle-, brain- and Purkinje cell-promoters) was completely abolished in the myocardium, while the brain- and Purkinje cell- (but not the muscle-) isoforms were detectable in the skeletal muscle. Immunocytochemical studies with anti-dystrophin antibodies showed that the protein was reduced in quantity but normally distributed in the skeletal muscle, while it was undetectable in the cardiac muscle. These findings indicate that expression of the muscle dystrophin isoform is critical for myocardial function and suggest that selective heart involvement in dystrophin-linked dilated cardiomyopathy is related to the absence, in the heart, of a compensatory expression of dystrophin from alternative promoters.
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PMID:A point mutation in the 5' splice site of the dystrophin gene first intron responsible for X-linked dilated cardiomyopathy. 878 42

To identify Chinese geneticists' views of ethical issues in genetic testing and screening, a national survey was conducted. Of 402 Chinese geneticists asked to participate, 255 (63%) returned by mail anonymous questionnaires. The majority of respondents thought that genetic testing should be offered in the workplace for alpha-antitrypsin deficiency (95%) and the predisposition of executives to heart disease, cancer, and diabetes (94%); that genetic testing should be included in preemployment physical examinations (86%); that governments should require premarital carrier tests (86%), newborn screening for sickle cell (77%), and Duchenne muscular dystrophy (71%); and that children should be tested for genes for late-onset disorders such as Huntington disease (85%), susceptibility to cancers (85%), familial hypercholesterolemia (84%), alcoholism (69%), and Alzheimer disease (61%). Most believed that partners should know each other's genetic status before marriage (92%), that carriers of the same defective gene should not mate with each other (91%), and that women should have a prenatal diagnosis if medically indicated (91%). The majority said that in China decisions about family planning were shared by the couple (82%). More than half had views that, in China, there were no laws to prohibit disability discrimination (64%), particularly to protect people with adult polycystic kidney disease (57%), cystic fibrosis (56%), or genetic predisposition to other diseases (50%). To some extent, these results might provide a basis for a discussion of eugenics in China, particularly about China's Maternal and Infant Health Care Law (1994).
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PMID:Chinese geneticists' views of ethical issues in genetic testing and screening: evidence for eugenics in China. 1048 40

A subset of patients harboring mutations in the dystrophin gene suffer from X-linked dilated cardiomyopathy (XLCM), a familial heart disease that is not accompanied by any clinical signs of skeletal muscle myopathy. As the muscle (M) isoform of dystrophin is not expressed in these patients, the absence of skeletal muscle symptoms has been attributed to expression of the brain (B) and cerebellar Purkinje (CP) isoforms of dystrophin in skeletal, but not cardiac, muscles of XLCM patients. The compensatory mechanism of dystrophin B and CP promoter upregulation is not known but it has been suggested that the dystrophin muscle enhancer from intron 1, DME-1, may be important in this activity. Previous studies have shown that the presence of the DME-1 is essential for a significant increase in dystrophin B and CP promoter activity in skeletal muscle cells in culture. Here, we demonstrate that the mouse dystrophin CP promoter drives expression of a lacZ reporter gene specifically to the cerebellar Purkinje cell layer but not to skeletal or cardiac muscle of transgenic mice. However, if the mouse counterpart of DME-1 is present in the transgene construct, the dystrophin CP promoter is now activated in skeletal muscle, but not in cardiac muscle. Our findings provide in vivo evidence for the importance of the dystrophin muscle enhancer sequences in activating the dystrophin CP promoter in skeletal muscle. Furthermore, they provide support for the model in which muscle enhancers, like DME-1, activate the dystrophin B and CP promoters in skeletal muscle, but not in cardiac muscle, of XLCM patients.
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PMID:The mouse dystrophin muscle enhancer-1 imparts skeletal muscle, but not cardiac muscle, expression onto the dystrophin Purkinje promoter in transgenic mice. 1538 45

Cardiomyopathy is a frequent occurrence in muscular dystrophy, and heart disease in muscular dystrophy can contribute to both morbidity and mortality. A number of novel therapies are being developed for muscular dystrophy, and the efficacy of these therapies for heart disease is unknown. The most common X-linked recessive disease is Duchenne muscular dystrophy (DMD), which arises from defects in the dystrophin gene. Therapy specifically aimed at DMD is reviewed in the context of its projected effect on cardiomyopathy associated with DMD. Additionally, novel therapies are being pursued to treat specifically the cardiomyopathy of DMD. There is substantial genetic heterogeneity underlying the muscular dystrophies, and not all muscular dystrophy patients develop cardiomyopathy. A subset of muscular dystrophies may place patients at significantly greater risk of developing cardiomyopathy and cardiac rhythm disturbances. These disorders are discussed, highlighting recent studies and recommendations for therapy.
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PMID:New approaches in the therapy of cardiomyopathy in muscular dystrophy. 1721 26


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