title: Multiple exon skipping strategies to by-pass dystrophin mutations.
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.
authors.affiliation: Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Carl F
authors.initials: CF
authors.lastname: Adkin
authors.forename: Penelope L
authors.initials: PL
authors.lastname: Meloni
authors.forename: Susan
authors.initials: S
authors.lastname: Fletcher
authors.forename: Abbie M
authors.initials: AM
authors.lastname: Adams
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
authors.forename: Brenda
authors.initials: B
authors.lastname: Wong
authors.forename: Steve D
authors.initials: SD
authors.lastname: Wilton
mesh_terms: D002478:Cells, Cultured; D016189:Dystrophin / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000628:therapy*; D009154:Mutation / Q000235:genetics*; D016376:Oligonucleotides, Antisense / Q000235:genetics; D016364:Reading Frames / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D016189:Dystrophin; D016376:Oligonucleotides, Antisense