Restoration of the normal splicing pattern of the PLP1 gene by means of an antisense oligonucleotide directed against an exonic mutation

Regis, Stefano, Corsolini, Fabio, Grossi, Serena, Tappino, Barbara, Cooper, David Neal ORCID: https://orcid.org/0000-0002-8943-8484 and Filocamo, Mirella 2013. Restoration of the normal splicing pattern of the PLP1 gene by means of an antisense oligonucleotide directed against an exonic mutation. PLoS One 8 (9) , e73633.. 10.1371/journal.pone.0073633

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Abstract

An exonic missense mutation, c.436C>G, in the PLP1 gene of a patient affected by the hypomyelinating leukodystrophy, Pelizaeus–Merzbacher disease, has previously been found to be responsible for the alteration of the canonical alternative splicing profile of the PLP1 gene leading to the loss of the longer PLP isoform. Here we show that the presence of the c.436C>G mutation served to introduce regulatory motifs that appear to be responsible for the perturbed splicing pattern that led to loss of the major PLP transcript. With the aim of disrupting the interaction between the PLP1 splicing regulatory motifs and their cognate splicing factors, we designed an antisense oligonucleotide-based in vitro correction protocol that successfully restored PLP transcript production in oligodendrocyte precursor cells.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > R Medicine (General)
Additional Information:	© 2013 Regis et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Publisher:	Public Library of Science
ISSN:	1932-6203
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	30 July 2013
Last Modified:	04 May 2023 06:50
URI:	https://orca.cardiff.ac.uk/id/eprint/84037

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