Multiple Exon Skipping Strategies to By-pass Dystrophin Mutations

Overview

Journal Neuromuscul Disord

Specialty Neurology

Date 2011 Dec 21

PMID 22182525

Citations 7

Authors

Carl F Adkin

Penelope L Meloni

Susan Fletcher

Abbie M Adams

Francesco Muntoni

Brenda Wong

Steve D Wilton

Affiliations

Soon will be listed here.

Abstract

Manipulation of dystrophin pre-mRNA processing offers the potential to overcome mutations in the dystrophin gene that would otherwise lead to Duchenne muscular dystrophy. Dystrophin mutations will require the removal of one or more exons to restore the reading frame and in some cases, multiple exon skipping strategies exist to restore dystrophin expression. However, for some small intra-exonic mutations, a third strategy, not applicable to whole exon deletions, may be possible. The removal of only one frame-shifting exon flanking the mutation-carrying exon may restore the reading frame and allow synthesis of a functional dystrophin isoform, providing that no premature termination codons are encountered. For these mutations, the removal of only one exon offers a simpler, cheaper and more feasible alternative approach to the dual exon skipping that would otherwise be considered. We present strategies to by-pass intra-exonic dystrophin mutations that clearly demonstrate the importance of tailoring exon skipping strategies to specific patient mutations.

Citing Articles

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Exon 32 Skipping of Dysferlin Rescues Membrane Repair in Patients' Cells.

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