DUCHENNE MUSCULAR DYSTROPHY AND BECKER MUSCULAR DYSTROPHY
Duchenne muscular dystrophy and Becker muscular dystrophy can be caused by deletions, duplications or point mutations in the DMD gene that encodes dystrophin. Information on DMD and the various deletions/duplications in this gene can be found on www.dmd.nl. To what extent DMD manifests depends on whether the translational reading frame is lost or maintained. Partial gene deletions or duplications in the DMD gene accounts for as much as ~65% of cases of these dystrophies. This extremely high percentage may be due to the nature of the protein and the gene’s extreme length (> 2.2 Mb).
This P034/P035 DMD probemix contains probes for each of the exons of the DMD gene on Xp21.2 chromosome. In addition, one probe is present for the alternative exon 1 DP427c. These 80 probes have been divided in two probe mixes: P034 and P035. Performing two MLPA reactions is thus sufficient to investigate the copy number of all exons.
Since MLPA offers a more extensive screening than many other methods used in DMD analysis, you may find deletions/duplications that were previously overlooked. For instance, we have been notified by one customer that among 33 samples that were initially found to be normal using the widely used deletion multiplex test, 6 samples were actually found to be positive with MLPA (18.1%); 4 of these were duplications and the other 2 had deletions which are not covered by the multiplex PCR test. Schwartz, M et al. (2007) have reported a completely healthy male with a deletion of exon 16 and part of introns 15 and 16. Their findings suggest that even large gene re-arrangements of the dystrophin gene may not always be disease-causing. Please be caution with the diagnosis of dystrophinopathy in sporadic cases of single exon in-frame deletions.