Ítem
Solo Metadatos

Mutant GNLY is linked to Stevens–Johnson syndrome and toxic epidermal necrolysis

Mostrar el registro sencillo de la publicación
dc.creatorFonseca Mendoza, Dora Janethspa
dc.creatorCaro L.A.spa
dc.creatorSierra-Díaz D.C.spa
dc.creatorSerrano-Reyes C.spa
dc.creatorLondoño O.spa
dc.creatorSuárez Y.C.spa
dc.creatorMateus H.E.spa
dc.creatorBolívar-Salazar D.spa
dc.creatorRamírez A.F.spa
dc.creatorde-la-Torre, Alejandraspa
dc.creatorLaissue P.spa
dc.date.accessioned2020-05-26T00:10:11Z
dc.date.available2020-05-26T00:10:11Z
dc.date.created2019spa
dc.description.abstractStevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions to drugs. Granulysin (GNLY) plays a key role in keratinocyte apoptosis during SJS/TEN pathophysiology. To determine if GNLY-encoding mutations might be related to the protein’s functional disturbances, contributing to SJS/TEN pathogenesis, we performed direct sequencing of GNLY’s coding region in a group of 19 Colombian SJS/TEN patients. A GNLY genetic screening was implemented in a group of 249 healthy individuals. We identified the c.11G > A heterozygous sequence variant in a TEN case, which creates a premature termination codon (PTC) (p.Trp4Ter). We show that a mutant protein is synthesised, possibly due to a PTC-readthrough mechanism. Functional assays demonstrated that the mutant protein was abnormally located in the nuclear compartment, potentially leading to a toxic effect. Our results argue in favour of GNLY non-synonymous sequence variants contributing to SJS/TEN pathophysiology, thereby constituting a promising, clinically useful molecular biomarker. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1007/s00439-019-02066-w
dc.identifier.issn03406717
dc.identifier.issn14321203
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/24215
dc.language.isoengspa
dc.publisherSpringerspa
dc.relation.citationEndPage1274
dc.relation.citationIssueNo. 44176
dc.relation.citationStartPage1267
dc.relation.citationTitleHuman Genetics
dc.relation.citationVolumeVol. 138
dc.relation.ispartofHuman Genetics, ISSN:03406717, 14321203, Vol.138, No.44176 (2019); pp. 1267-1274spa
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85074025514&doi=10.1007%2fs00439-019-02066-w&partnerID=40&md5=1b915c3775dff3aa10c0cb5a8493e13bspa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subject.keywordCarbamazepinespa
dc.subject.keywordpreschooleng
dc.subject.keyworddifferentiationeng
dc.subject.keywordCefalexinspa
dc.subject.keywordhumaneng
dc.subject.keywordCocodamolspa
dc.subject.keywordt-lymphocyteeng
dc.subject.keywordContrast mediumspa
dc.subject.keywordCotrimoxazolespa
dc.subject.keywordGranulysinspa
dc.subject.keywordLamotriginespa
dc.subject.keywordMetoclopramidespa
dc.subject.keywordPhenytoinspa
dc.subject.keywordPyrimethamine plus sulfadoxinespa
dc.subject.keywordSulfonamidespa
dc.subject.keywordBiological markerspa
dc.subject.keywordGnly proteineng
dc.subject.keywordMutant proteinspa
dc.subject.keywordT lymphocyte antigenspa
dc.subject.keywordAdultspa
dc.subject.keywordAnimal cellspa
dc.subject.keywordArticlespa
dc.subject.keywordCellular distributionspa
dc.subject.keywordChildspa
dc.subject.keywordCho cell linespa
dc.subject.keywordClinical articlespa
dc.subject.keywordCodonspa
dc.subject.keywordComputer modelspa
dc.subject.keywordFemalespa
dc.subject.keywordGene frequencyspa
dc.subject.keywordGene mutationspa
dc.subject.keywordGene sequencespa
dc.subject.keywordHeterozygotespa
dc.subject.keywordHumanspa
dc.subject.keywordMalespa
dc.subject.keywordMiddle agedspa
dc.subject.keywordNonhumanspa
dc.subject.keywordNucleotide sequencespa
dc.subject.keywordPathogenesisspa
dc.subject.keywordPathophysiologyspa
dc.subject.keywordPreschool childspa
dc.subject.keywordPriority journalspa
dc.subject.keywordProtein localizationspa
dc.subject.keywordSanger sequencingspa
dc.subject.keywordSchool childspa
dc.subject.keywordStevens johnson syndromespa
dc.subject.keywordToxic epidermal necrolysisspa
dc.subject.keywordUrtica dioicaspa
dc.subject.keywordWestern blottingspa
dc.subject.keywordYoung adultspa
dc.subject.keywordAdolescentspa
dc.subject.keywordApoptosisspa
dc.subject.keywordCase control studyspa
dc.subject.keywordGenetic predispositionspa
dc.subject.keywordGeneticsspa
dc.subject.keywordInfantspa
dc.subject.keywordKeratinocytespa
dc.subject.keywordMetabolismspa
dc.subject.keywordMutationspa
dc.subject.keywordNecrosisspa
dc.subject.keywordPathologyspa
dc.subject.keywordStevens johnson syndromespa
dc.subject.keywordAdolescentspa
dc.subject.keywordAdultspa
dc.subject.keywordAntigenseng
dc.subject.keywordApoptosisspa
dc.subject.keywordBiomarkersspa
dc.subject.keywordCase-control studiesspa
dc.subject.keywordChildspa
dc.subject.keywordChildeng
dc.subject.keywordFemalespa
dc.subject.keywordGenetic predisposition to diseasespa
dc.subject.keywordHumansspa
dc.subject.keywordInfantspa
dc.subject.keywordKeratinocytesspa
dc.subject.keywordMalespa
dc.subject.keywordMiddle agedspa
dc.subject.keywordMutant proteinsspa
dc.subject.keywordMutationspa
dc.subject.keywordNecrosisspa
dc.subject.keywordStevens-johnson syndromespa
dc.subject.keywordYoung adultspa
dc.titleMutant GNLY is linked to Stevens–Johnson syndrome and toxic epidermal necrolysisspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
Archivos
Colecciones
Artículos