Résumé :
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The severe Duchenne muscular dystrophy (DMD) and the milder Becker muscular dystrophy (BMD) are characterized by progressive muscular degeneration. Both are caused by mutations in the dystrophin gene (Xp21.2). Two thirds of patients show intragenic deletions of one to several exons, the remaining cases arise from genomic duplication or microrearrangements. The reading frame rule explains the two different phenotypes resulting from mutations in the same gene. Clinical progression of the disease can be predicted by whether the deletion maintains (in frame-BMD) or disrupts (out of frame-DMD) the translational reading frame of the dystrophin gene. This hypothesis explains the phenotypic differences observed in approximately 92% of the DMD/BMD cases. We report a Becker muscular dystrophy family with one 5-year-old affected patient and his 69-year-old asymptomatic grandfather. Dystrophin gene multiplex PCR and MLPA analyses showed that both males carry an in-frame deletion of exons 45-55. Molecular analysis of different tissues and elevated serum creatin kinase (CK) levels, ruled out a germline mosaicism in the grandfather. Segregation analysis revealed two additional asymptomatic boys with the same deletion and 4 deletion-carrier females. These results show that the deletion of exons 45-55 found in the family is associated with a mild or asymptomatic phenotype. Our findings support previous prediction of being exons 45-55 the optimal multiexon skipping target in antisense gene therapy to transform the Duchenne muscular dystrophy phenotype into a Becker or even asymptomatic phenotype. The screening of 170 DMD-deletions, already analysed by us, resulted in the finding of 45% of them being included in the region of exons 45-55. Therefore, the patients with these deletions would be benefited with the antisense therapy to acquire a mild or even asymptomatic phenotype.
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