Article: Exon skipping through the creation of a putative exonic splicing silencer as a consequence of the cystic fibrosis mutation R553X

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TitleExon skipping through the creation of a putative exonic splicing silencer as a consequence of the cystic fibrosis mutation R553X
AuthorsAznarez, I3
Zielenski, J3
Rommens, JM3
Blencowe, BJ2
Tsui, LC1
Issue Date2007
PublisherBMJ Group. The Journal's web site is located at http://jmg.bmj.com/
CitationJournal Of Medical Genetics, 2007, v. 44 n. 5, p. 341-346 [How to Cite?]
DOI: http://dx.doi.org/10.1136/jmg.2006.045880
AbstractNonsense mutations that occur more than 50 bases upstream of terminal spliced junctions are generally thought to lead to degradation of the corresponding transcripts by the process of nonsense-mediated mRNA decay. It has also been proposed that some nonsense mutations may affect splicing by the process of nonsense-associated altered splicing (NAS), or by the disruption of a splicing regulatory element. In this study, the effect of the R553X mutation on the splicing of exon 11 of the cystic fibrosis transmembrane conductance regulator gene was investigated. Evidence that R553X causes exon 11 to skip through the creation of a putative exonic splicing silencer (ESS) was provided. The putative ESS appears to be active when located immediately upstream of a 5′ splice site. These findings argue against the possibility that R553X-associated exon 11 skipping is caused by NAS. The study further suggests that aminoglycoside antibiotic treatment would not be effective for patients with the R553X mutation, owing to the skipping of exon 11, and further emphasises the need for detailed mechanistic characterisation of the consequences of nonsense disease mutations.
ISSN0022-2593
2011 Impact Factor: 6.365
2011 SCImago Journal Rankings: 0.841
DOIhttp://dx.doi.org/10.1136/jmg.2006.045880
ISI Accession Number IDWOS:000246177200008
PubMed Central IDPMC2597982
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorAznarez, I
dc.contributor.authorZielenski, J
dc.contributor.authorRommens, JM
dc.contributor.authorBlencowe, BJ
dc.contributor.authorTsui, LC
dc.date.accessioned2011-11-01T04:09:22Z
dc.date.available2011-11-01T04:09:22Z
dc.date.issued2007
dc.description.abstractNonsense mutations that occur more than 50 bases upstream of terminal spliced junctions are generally thought to lead to degradation of the corresponding transcripts by the process of nonsense-mediated mRNA decay. It has also been proposed that some nonsense mutations may affect splicing by the process of nonsense-associated altered splicing (NAS), or by the disruption of a splicing regulatory element. In this study, the effect of the R553X mutation on the splicing of exon 11 of the cystic fibrosis transmembrane conductance regulator gene was investigated. Evidence that R553X causes exon 11 to skip through the creation of a putative exonic splicing silencer (ESS) was provided. The putative ESS appears to be active when located immediately upstream of a 5′ splice site. These findings argue against the possibility that R553X-associated exon 11 skipping is caused by NAS. The study further suggests that aminoglycoside antibiotic treatment would not be effective for patients with the R553X mutation, owing to the skipping of exon 11, and further emphasises the need for detailed mechanistic characterisation of the consequences of nonsense disease mutations.
dc.description.naturepublished_or_final_version
dc.identifier.citationJournal Of Medical Genetics, 2007, v. 44 n. 5, p. 341-346 [How to Cite?]
DOI: http://dx.doi.org/10.1136/jmg.2006.045880
dc.identifier.doihttp://dx.doi.org/10.1136/jmg.2006.045880
dc.identifier.epage346
dc.identifier.isiWOS:000246177200008
dc.identifier.issn0022-2593
2011 Impact Factor: 6.365
2011 SCImago Journal Rankings: 0.841
dc.identifier.issue5
dc.identifier.openurl
dc.identifier.pmcidPMC2597982
dc.identifier.pmid17475917
dc.identifier.scopuseid_2-s2.0-34248368508
dc.identifier.spage341
dc.identifier.urihttp://hdl.handle.net/10722/143112
dc.identifier.volume44
dc.languageeng
dc.publisherBMJ Group. The Journal's web site is located at http://jmg.bmj.com/
dc.publisher.placeUnited Kingdom
dc.relation.ispartofJournal of Medical Genetics
dc.relation.referencesReferences in Scopus
dc.rightsJournal of Medical Genetics. Copyright © BMJ Group.
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
dc.subject.meshAlternative Splicing - genetics
dc.subject.meshArginine - genetics
dc.subject.meshCystic Fibrosis - genetics
dc.subject.meshCystic Fibrosis Transmembrane Conductance Regulator - genetics
dc.subject.meshExons - genetics
dc.titleExon skipping through the creation of a putative exonic splicing silencer as a consequence of the cystic fibrosis mutation R553X
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong
  2. University of Toronto
  3. Hospital for Sick Children, Toronto