A simple explanation for a case of incompatibility with the reading frame theory in Duchenne muscular dystrophy: failure to detect an aberrant restriction fragment in Southern blot analysis

According to the translational reading frame theory, Duchenne muscular dystrophy (DMD) patients harbor out-of-frame deletion mutations in the dystrophin gene. We identified a Japanese DMD case who appeared to have an in-frame deletion of exons 46–54 that was disclosed by Southern blot analysis using a dystrophin cDNA as a probe. Analysis of dystrophin mRNA in skeletal muscle revealed the presence of an out-of-frame deletion of exons 46–53. In agreement with this result, the region encompassing exon 54 could be amplified from genomic DNA by polymerase chain reaction (PCR). Furthermore, re-analysis by Southern blot using an exon specific probe disclosed that a HindIII fragment containing exon 54 was present at aberrant size, leading to the incorrect conclusion that exon 54 had been deleted. Thus, this particular DMD case does not constitute an exception to the reading frame theory.