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Exceptions to exceptions in the Duchenne: Becker dystrophin reading frame

Krishnaswamy, S., Fletcher, S., Wong, B.L. and Wilton, S.D. (2013) Exceptions to exceptions in the Duchenne: Becker dystrophin reading frame. The Journal of Gene Medicine, 15 (8-9). p. 336.

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The majority of mutations in the dystrophin gene lead to either a severe condition, Duchenne muscular dystrophy, or a milder allelic condition Becker muscular dystrophy. The dystrophin reading frame generally correlates disease severity with the genotype, but there are notable exceptions in about 10% of cases. Dystrophin protein truncating mutations have been described that manifest with only mild symptoms, while in - frame deletions may present with an unexpectedly severe phenotype. One such exception to the reading frame rule is the deletion of dystrophin exon 5, an in - frame deletion that has been reported to manifests a Duchenne muscular dystrophy. The severe phenotype in two unrelated dystrophin exon 5 deletion patients was attributed to the deletion of both exons 5 and 6 from the mature mRNA, with disruption of the reading frame. Here, we describe a patient with a genomic deletion of dystrophin exon 5 who presents with relatively mild symptoms. Unlike the cases reported above, the mRNA transcribed from this mutation retained exon 6. Deletion breakpoint mapping indicated that part of introns 4 and 5 were also deleted from the genomic DNA and the deletion was larger than other deletions reported around this exon. Application of a splice switching oligomer targeting dystrophin exon 6 removed that exon from the mature mRNA at efficiencies similar to that observed following testing in normal myogenic cells, indicating this particular loss of dystrophin exon 5 did not compromise exon 6 recognition. It is evident that not all dystrophin genomic deletions are processed in a similar manner.

Item Type: Journal Article
Murdoch Affiliation: Centre for Comparative Genomics
Publisher: Wiley
Copyright: © 2013 John Wiley & Sons, Ltd.
Notes: Conference abstract
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