In Vitro Correction of a Pseudoexon‐Generating Deep Intronic Mutation in LGMD2A by Antisense Oligonucleotides and Modified Small Nuclear RNAs. Issue 10 (7th August 2013)

• Record Type: Journal Article
• Authors: Blázquez, Lorea; Aiastui, Ana; Goicoechea, Maria; Martins de Araujo, Mafalda; Avril, Aurélie; Beley, Cyriaque; García, Luis; Valcárcel, Juan; Fortes, Puri; López de Munain, Adolfo
• Is Part Of: Human mutation. Volume 34:Issue 10(2013:Oct.)
• Page Start: 1387
• Page End: 1395
• Publication Date: 2013-08-07
• Subjects: Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.22379
• Languages: English
• ISSNs: 1059-7794

Abstract

<abstract abstract-type="graphical" xml:lang="en" id="humu22379-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>c.1782+1072G&gt;C mutation is the first deep‐intronic mutation in the CAPN3 gene, which leads to LGMD2A. The mutation causes the inclusion of a pseudoexon in mature CAPN3 mRNA. In this work, we demonstrate mutation pathogenicity with a minigene assay and we induce splicing modulation with Antisense Oligonucleotides (AONs) and modified U‐snRNAs. In addition, AON treatment restores correct splicing in fibroblasts from a LGMD2A patient which harbors this mutation. Our results indicate that SRSF1 splicing factor is involved in pseudoexon activation. <boxed-text content-type="graphic" position="anchor" orientation="portrait"><graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgg3hnbnkjv" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></boxed-text></p> </abstract>