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

A young woman with humeroperoneal muscular dystrophy and contractures received a heart transplant for a severe dilated cardiomyopathy. Cardiac histopathology consisted of myocyte hypertrophy, interstitial fibrosis, and nuclear hyperchromaticity without mitochondrial abnormalities. Myopathy and heart disease were not clinically evident in her family, although three relatives had unexplained shortened Achilles tendons without weakness. Tendon contractures may be a partial expression of this myopathic disorder, suggesting an autosomal dominant inheritance with variable penetrance. A muscular dystrophy clinically similar to that of the Emery-Dreifuss (EDMD) type can thus occur in women. Rather than the cardiac arrhythmias typical of EDMD, a dilated cardiomyopathy may occur and present with severe congestive heart failure. This is the first report of cardiac transplantation in such a case.
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PMID:Cardiac transplantation in female Emery-Dreifuss muscular dystrophy. 223 Aug 49

Emery-Dreifuss muscular dystrophy (EDMD) is an inherited disorder characterized by slowly progressive skeletal muscle weakness in a humero-peroneal distribution, early contractures and prominent cardiomyopathy with conduction block. Mutations in EMD, encoding emerin, and LMNA, encoding A-type lamins, respectively, cause X-linked and autosomal dominant EDMD. Emerin and A-type lamins are proteins of the inner membrane of the nuclear envelope. Whereas the genetic cause of EDMD has been described and the proteins well characterized, little is known on how abnormalities in nuclear envelope proteins cause striated muscle disease. In this study, we analyzed genome-wide expression profiles in hearts from Emd knockout mice, a model of X-linked EDMD, using Affymetrix GeneChips. This analysis showed a molecular signature similar to that we previously described in hearts from Lmna H222P knock-in mice, a model of autosomal dominant EDMD. There was a common activation of the ERK1/2 branch of the mitogen-activated protein kinase (MAPK) pathway in both murine models, as well as activation of downstream targets implicated in the pathogenesis of cardiomyopathy. Activation of MAPK signaling appears to be a cornerstone in the development of heart disease in both X-linked and autosomal dominant EDMD.
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PMID:Activation of MAPK in hearts of EMD null mice: similarities between mouse models of X-linked and autosomal dominant Emery Dreifuss muscular dystrophy. 1756 79

The human genome is contained within the nucleus and is separated from the cytoplasm by the nuclear envelope. Mutations in the nuclear envelope proteins emerin and lamin A cause a number of diseases including premature aging syndromes, muscular dystrophy, and cardiomyopathy. Emerin and lamin A are implicated in regulating muscle- and heart-specific gene expression and nuclear architecture. For example, lamin A regulates the expression and localization of gap junction and intercalated disc components. Additionally, emerin and lamin A are also required to maintain nuclear envelope integrity. Demonstrating the importance of maintaining nuclear integrity in heart disease, atrioventricular node cells lacking lamin A exhibit increased nuclear deformation and apoptosis. This review highlights the present understanding of lamin A and emerin function in regulating nuclear architecture, gene expression, and cell signaling and discusses putative mechanisms for how specific mutations in lamin A and emerin cause cardiac- or muscle-specific disease.
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PMID:Emerin and the nuclear lamina in muscle and cardiac disease. 1859 64