We have studied two Duchenne patients carrying the in-frame isolated deletion of dystrophin exon 5 and we have defined the genomic deletion breakpoints. Transcription analysis in skeletal muscle from one patient revealed a complex RNA configuration, combining an unfavorable exon skipping event (involving exon 6 and leading to an out-of-frame transcript) with the production of scrambled, circular RNA molecules. RNA circularization specifically involved the in-frame transcripts (retaining exon 6) with the consequence of depletion of the functional messenger. In addition, we also documented abundant in-frame exon 9 skipping. This peculiar splicing behavior leading to a defect in the in-frame messenger RNA and in critical protein domains, might represent the pathogenic background underlying the severe clinical impact of the rare exon 5 deletion. The circular molecule formation focuses attention on the role that RNA scrambling might have in contributing to the clinical severity in dystrophin deletions.

Multiple exon skipping and RNA circularisation contribute to the severe phenotypic expression of exon 5 dystrophin deletion.

GUALANDI, Francesca;TRABANELLI, Cecilia;RIMESSI, Paola;CALZOLARI, Elisa;FERLINI, Alessandra
2003

Abstract

We have studied two Duchenne patients carrying the in-frame isolated deletion of dystrophin exon 5 and we have defined the genomic deletion breakpoints. Transcription analysis in skeletal muscle from one patient revealed a complex RNA configuration, combining an unfavorable exon skipping event (involving exon 6 and leading to an out-of-frame transcript) with the production of scrambled, circular RNA molecules. RNA circularization specifically involved the in-frame transcripts (retaining exon 6) with the consequence of depletion of the functional messenger. In addition, we also documented abundant in-frame exon 9 skipping. This peculiar splicing behavior leading to a defect in the in-frame messenger RNA and in critical protein domains, might represent the pathogenic background underlying the severe clinical impact of the rare exon 5 deletion. The circular molecule formation focuses attention on the role that RNA scrambling might have in contributing to the clinical severity in dystrophin deletions.
2003
Gualandi, Francesca; Trabanelli, Cecilia; Rimessi, Paola; Calzolari, Elisa; Toffolatti, L; Patarnello, T; Kunz, G; Muntoni, F; Ferlini, Alessandra
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/470471
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