Role of splicing factor in muscular dystrophies

Role of splicing factor in muscular dystrophies

 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.