Titre :
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Dystrophinopathies and X-inactivation pattern : about 26 symptomatic carriers at pediatric age
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contenu dans :
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Auteurs :
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4th International Congress of Myology, 4ème colloque international de Myologie (9-13 mai 2011; Lille (France)) ;
Mercier S ;
Toussaint A ;
Beugnet C ;
De Barace C ;
Toutain A ;
Raynaud M ;
Marcorelles P ;
Pasquier L ;
Chauvel-Lebreton J ;
Benyaou R ;
France L ;
Chelly J ;
Desguerre I
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Type de document :
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Article
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Année de publication :
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2011
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Pages :
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p. 79
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Langues:
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Anglais
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Mots-clés :
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colloque
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Résumé :
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Aim: to define molecular basis underlying different clinical phenotypes and of symptomatic DMD carriers at pediatric age.Methods: 26 cases of early symptomatic DMDcarriers followed in the french neuromuscular network were investigated. We report findings concerning clinical presentation, muscular histological analysis and type ofgene mutation, as well as study X-chromosome inactivation patterns using DNA extracted from peripheral blood or muscle.Results: The initial symptoms were significantweakness (88%) or exercise intolerance (27%). Clinical severity varied from a Duchenne-like progression to a very mild Becker-like phenotype. Cardiac dysfunctionwas present in 19% of the cases. Cognitive impairment was worthy of notice as 23% of the carriers are concerned. The muscular analysis was always contributiverevealing muscular dystrophy (83%), mosaic in immunostaining (81%) and dystrophin abnormalities in Western Blot analysis (84%). 73% had exonic deletions orduplications and 27% had point mutations. The X-chromosome inactivation pattern was skewed toward non-random in 62% of the cases i.e. 10 informative deletions orduplications/triplication and 3 nonsense or skipping mutations.Interpretation: We report the largest series of manifesting DMD carriers and show that exercise intoleranceand cognitive impairment may reveal symptomatic DMD carriers. The complete histological and immunohistological study of the muscle is the key of the diagnosisleading to the dystrophin gene analysis. Our study shows also that cognitive impairment in symptomatic DMD carriers is associated with mutations in the distal part ofthe DMD gene. The study of the X-chromosome inactivation pattern does not fully explain the mechanisms as well as the wide spectrum of clinical phenotype, though aclear correlation between the severity of the phenotype and inactivation bias was observed.
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