Predicted and observed sizes of dystrophin in some patients with gene deletions that disrupt the open reading frame.

L V Nicholson, K M Bushby, M A Johnson, J T den Dunnen, I B Ginjaar, G J van Ommen

Muscular Dystrophy Group Research Laboratories, Newcastle General Hospital, Newcastle upon Tyne.

Among 85 patients with Duchenne and Becker muscular dystrophy, 29 were found to have mutations which disrupted the open reading frame for dystrophin. Thus any dystrophin detected in this group of patients should consist of the severely truncated polypeptides that represent prematurely terminated translation products. Dystrophin was detected in blots from 17/29 biopsies and the observed sizes of the polypeptides were compared with predicted sizes calculated in two ways: if translation was terminated at the stop codon generated by each frameshifting deletion, and if the reading frame was restored and translation proceeded. In every case the observed size matched the size predicted on the basis of a restored reading frame. This was in accord with immunocytochemical labelling of scattered dystrophin positive fibres which were found on serial sections labelled with antibodies to both the rod and C-terminal domains. Thus analysis at the protein level supports genetic evidence of exon skipping as a mechanism which restores frameshifting mutations in some fibres.

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