Substitutions, deletions and duplications in the dystrophin gene lead to either the severe Duchenne muscular dystrophy (DMD) or mild Becker muscular dystrophy depending on whether out-of-frame or in-frame transcripts are produced.
Researchers identified a DMD case (GSΔ44) where the correlation between genotype and phenotype is not respected, even if carrying a typical Duchenne mutation (exon 44 deletion) a Becker-like phenotype was observed.
They report that in this patient, partial restoration of an in-frame transcript occurs by natural skipping of exon 45 and that this is due to the lack of Celf2a, a splicing factor that interacts with exon 45 in the dystrophin pre-mRNA.
Several experiments are presented that demonstrate the central role of Celf2a in controlling exon 45 splicing; the data point to this factor as a potential target for the improvement of those DMD therapeutic treatments, which requires exon 45 skipping.
http://www.nature.com/ncomms/2016/160122/ncomms10488/full/ncomms10488.html
Role of splicing factor in muscular dystrophies
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