X-linked dilated cardiomyopathy and the dystrophin gene.
X-linked dilated cardiomyopathy (XLDC) represents a well known genetic disease, allelic to Duchenne and Becker muscular dystrophies and caused by dystrophin gene mutations. XLDC is a rare disease and only few families have been fully characterised. In several of them, the dystrophin mutations show a different pattern of expression in cardiac compared to skeletal muscle. In the families with the most severe cardiac phenotype, the cardiac muscle is usually unable to produce dystrophin, due to a specific effect that the mutation(s) have on the gene transcription in this tissue. The skeletal muscle escapes the dystrophic changes by maintaining dystrophin synthesis via exon skipping or alternative splicing that the heart is not able to put in place. In this paper we have reviewed the families with X-linked dilated cardiomyopathy reported so far; in addition we provided novel transcription data on two families we previously described. The aim of this review is to attempt a genotype-phenotype correlation and speculate on common pathogenic mechanisms underlying this disease.
Department of Paediatrics and Neonatal Medicine, Imperial College of Medicine, London, UK. aferlini@rpms.ac.uk
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Ferlini
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Sewry
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Melis
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Mateddu
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Muntoni
D000293:Adolescent; D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D003598:Cytoskeletal Proteins / Q000032:analysis; D018076:DNA, Complementary / Q000235:genetics; D016189:Dystrophin / Q000032:analysis / Q000235:genetics*; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000032:analysis; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D009154:Mutation; D009206:Myocardium / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics; D049031:Sarcoglycans; D012508:Sarcolemma / Q000737:chemistry; D049411:Utrophin; D014960:X Chromosome / Q000235:genetics*
D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D016189:Dystrophin; D007797:Laminin; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D020033:Protein Isoforms; D049031:Sarcoglycans; D049411:Utrophin; C102645:laminin alpha 2