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 dyst rophy (DMD) patients harbor out-of-frame deletion mutations in the dystroph in 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 musc le revealed the presence of an out-of-frame deletion of exons 46-53. In agr eement with this result, the region encompassing exon 54 could be amplified from genomic DNA by polymerase chain reaction (PCR). Furthermore, re-analy sis by Southern blot using an exon specific probe disclosed that a HindIII fragment containing exon 54 was present at aberrant size, leading to the in correct conclusion that exon 54 had been deleted. Thus, this particular DMD case does not constitute an exception to the reading frame theory. (C) 199 9 Elsevier Science B.V. All rights reserved.