Titre :
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Somatic and germinal mosaicism of a deletion in the dystrophin gene in an adult male patient with predominant dilated cardiomyopathy (abstract : congrès international de Myologie, 2005)
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contenu dans :
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Auteurs :
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Congrès international de myologie 2005 (International Congress of Myology 2005; 9-13 mai 2005; Nantes, France) ;
Hu Y ;
Eymard B ;
Laforet P ;
Heron D ;
Leturcq F ;
Llense S ;
Chelly J ;
Romero NB ;
Logeart D
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Type de document :
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Article
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Année de publication :
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2005
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Pages :
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p. 225
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Langues:
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Anglais
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Mots-clés :
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accident vasculaire cérébral
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adulte
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biopsie musculaire
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cardiomyopathie dilatée
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colloque
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créatine kinase
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dystrophine
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électromyographie
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épaule
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étude de cas
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faiblesse musculaire
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gène DMD
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immunofluorescence
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mosaïcisme germinal
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mosaïcisme somatique
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muscle squelettique
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mutation génétique
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myocarde
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tomodensitométrie
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transplantation cardiaque
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Résumé :
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Communication n° 714 A 50-year-old man without any family history presented a dilated cardiomyopathy, at the age of 41, discovered in the etiologic inquiry of an ischaemic cerebral stroke. From then on, he has suffered moderate asymmetric muscle weakness of the right shoulder (ICA sequel or dystrophy sign?). A moderately high creatine phosphokinase (CPK) level (500-1000 UI/L) was observed at the time of the pre-heart implantation due to the severe left ventricular dysfunction. An electromyogram and muscular tomodensitometry showed respectively diffuse myopathic changes and fatty amyotrophic lesions involving the right proximal limb muscles. QF-PCR multiplex indicates mosaicism (80%/ 20%) for an out of frame deletion of exon 49 to 52. A deltoid muscle biopsy evidenced a dy strophic pattern. An immunofluorescent study performed with different dystrophin-specific monoclonal antibodies showed only 1% dystrophin negative muscle fibres with anti-Dys2 antibody (C-term domain). Histological examinations of the myocardium after the heart transplantation revealed fatty and fibrous replacement of myocardiocytes with some areas of fibre hypertrophy. Dystrophin immunostaining of myocardial specimens showed a mosaic pattern of dystrophin-negative and positive fibres (30%-50% negative fibres). Western blot analysis of dystrophin showed a decreased amount in cardiac muscle while in skeletal muscle the level and the size of dystrophin were almost normal.His 4 daughters had no cardiac or muscular symptoms. However, the oldest da ughter presented also an increased CPK level and the multiplex PCR technique in the lymphocytes detected the same deletion of exons 49-52. His second daughter had no deletion in blood. On the whole, our data indicate that the mosaicism paternal for this deletion is not only somatic but also germinal. To our knowledge this is the first case of somatic and germinal mosaicism in an adult male patient with predominant cardiomyopathy involvement. Pathophysiological mechanisms will be discussed.
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