Document Detail

Genetic and clinical specificity of 26 symptomatic carriers for dystrophinopathies at pediatric age.
MedLine Citation:
PMID:  23299919     Owner:  NLM     Status:  MEDLINE    
The molecular basis underlying the clinical variability in symptomatic Duchenne muscular dystrophy (DMD) carriers are still to be precised. We report 26 cases of early symptomatic DMD carriers followed in the French neuromuscular network. Clinical presentation, muscular histological analysis and type of gene mutation, as well as X-chromosome inactivation (XCI) patterns using DNA extracted from peripheral blood or muscle are detailed. The initial symptoms were significant weakness (88%) or exercise intolerance (27%). Clinical severity varied from a Duchenne-like progression to a very mild Becker-like phenotype. Cardiac dysfunction was present in 19% of the cases. Cognitive impairment was worthy of notice, as 27% of the carriers are concerned. The muscular analysis was always contributive, revealing muscular dystrophy (83%), mosaic in immunostaining (81%) and dystrophin abnormalities in western blot analysis (84%). In all, 73% had exonic deletions or duplications and 27% had point mutations. XCI pattern was biased in 62% of the cases. In conclusion, we report the largest series of manifesting DMD carriers at pediatric age and show that exercise intolerance and cognitive impairment may reveal symptomatic DMD carriers. The complete histological and immunohistological study of the muscle is the key of the diagnosis leading to the dystrophin gene analysis. Our study shows also that cognitive impairment in symptomatic DMD carriers is associated with mutations in the distal part of the DMD gene. XCI study does not fully explain the mechanisms as well as the wide spectrum of clinical phenotype, though a clear correlation between the severity of the phenotype and inactivation bias was observed.
Sandra Mercier; Annick Toutain; Aurélie Toussaint; Martine Raynaud; Claire de Barace; Pascale Marcorelles; Laurent Pasquier; Martine Blayau; Caroline Espil; Philippe Parent; Hubert Journel; Leila Lazaro; Jon Andoni Urtizberea; Alexandre Moerman; Laurence Faivre; Bruno Eymard; Kim Maincent; Romain Gherardi; Denys Chaigne; Rabah Ben Yaou; France Leturcq; Jamel Chelly; Isabelle Desguerre
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Publication Detail:
Type:  Journal Article     Date:  2013-01-09
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  21     ISSN:  1476-5438     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-07-18     Completed Date:  2013-10-29     Revised Date:  2014-08-05    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  855-63     Citation Subset:  IM    
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MeSH Terms
Age of Onset
Blotting, Western
Child, Preschool
Cognition Disorders / genetics,  pathology
Dystrophin / genetics*,  metabolism
France / epidemiology
Middle Aged
Muscles / metabolism*,  pathology
Muscular Dystrophy, Duchenne / epidemiology,  genetics*,  pathology
X Chromosome Inactivation
Young Adult
Reg. No./Substance:
0/DMD protein, human; 0/Dystrophin
Erratum In:
Eur J Hum Genet. 2013 Aug;21(8):892

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