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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
2012 Impact Factor: 5.703
2012 SCImago Journal Rankings: 2.715
 
DOIhttp://dx.doi.org/10.1136/jmg.2006.045880
 
PubMed Central IDPMC2597982
 
ISI Accession Number IDWOS:000246177200008
 
ReferencesReferences in Scopus
 
DC FieldValue
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
2012 Impact Factor: 5.703
2012 SCImago Journal Rankings: 2.715
 
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
 
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Author Affiliations
  1. The University of Hong Kong
  2. University of Toronto
  3. Hospital for Sick Children University of Toronto