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. We 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. Here we 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; our data point to this factor as a potential target for the improvement of those DMD therapeutic treatments, which requires exon 45 skipping.

The lack of the Celf2a splicing factor converts a Duchenne genotype into a Becker phenotype / Martone, Julie; Briganti, F; Legnini, Ivano; Morlando, Mariangela; Picillo, E; Sthandier, Olga Elena; Politano, L; Bozzoni, Irene. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - STAMPA. - 7:(2016), pp. 1-8. [10.1038/ncomms10488]

The lack of the Celf2a splicing factor converts a Duchenne genotype into a Becker phenotype

MARTONE, Julie;Briganti, F;LEGNINI, IVANO;MORLANDO, MARIANGELA;STHANDIER, Olga Elena;BOZZONI, Irene
2016

Abstract

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. We 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. Here we 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; our data point to this factor as a potential target for the improvement of those DMD therapeutic treatments, which requires exon 45 skipping.
2016
Duchenne Muscular Distrophy; Celf2a; splicing
01 Pubblicazione su rivista::01a Articolo in rivista
The lack of the Celf2a splicing factor converts a Duchenne genotype into a Becker phenotype / Martone, Julie; Briganti, F; Legnini, Ivano; Morlando, Mariangela; Picillo, E; Sthandier, Olga Elena; Politano, L; Bozzoni, Irene. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - STAMPA. - 7:(2016), pp. 1-8. [10.1038/ncomms10488]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/850036
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