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Protein‐ and mRNA‐based phenotype–genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene
Author(s) -
Deburgrave Nathalie,
Daoud Fatma,
Llense Stéphane,
Barbot Jean Claude,
Récan Dominique,
Peccate Cécile,
Burghes Arthur H.M.,
Béroud Christophe,
Garcia Luis,
Kaplan JeanClaude,
Chelly Jamel,
Leturcq France
Publication year - 2007
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20422
Subject(s) - frameshift mutation , biology , nonsense mutation , dystrophin , point mutation , genetics , muscular dystrophy , exon , duchenne muscular dystrophy , mutation , phenotype , gene , microbiology and biotechnology , missense mutation
Straightforward detectable Duchenne muscular dystrophy (DMD) gene rearrangements, such as deletions or duplications involving an entire exon or more, are involved in about 70% of dystrophinopathies. In the remaining 30% a variety of point mutations or “small” mutations are suspected. Due to their diversity and to the large size and complexity of the DMD gene, these point mutations are difficult to detect. To overcome this diagnostic issue, we developed and optimized a routine muscle biopsy–based diagnostic strategy. The mutation detection rate is almost as high as 100% and mutations were identified in all patients for whom the diagnosis of DMD and Becker muscular dystrophy (BMD) was clinically suspected and further supported by the detection on Western blot of quantitative and/or qualitative dystrophin protein abnormalities. Here we report a total of 124 small mutations including 11 nonsense and frameshift mutations detected in BMD patients. In addition to a comprehensive assessment of muscular phenotypes that takes into account consequences of mutations on the expression of the dystrophin mRNA and protein, we provide and discuss genomic, mRNA, and protein data that pinpoint molecular mechanisms underlying BMD phenotypes associated with nonsense and frameshift mutations. Hum Mutat 28(2), 183–195, 2007. © 2006 Wiley‐Liss, Inc.