dc.creator | Fonseca-Mendoza, Dora Janeth | |
dc.creator | Caro L.A. | |
dc.creator | Sierra-Díaz D.C. | |
dc.creator | Serrano-Reyes C. | |
dc.creator | Londoño O. | |
dc.creator | Suárez Y.C. | |
dc.creator | Mateus H.E. | |
dc.creator | Bolívar-Salazar D. | |
dc.creator | Ramírez A.F. | |
dc.creator | de-la-Torre, Alejandra | |
dc.creator | Laissue P. | |
dc.date.accessioned | 2020-05-26T00:10:11Z | |
dc.date.accessioned | 2022-09-22T15:00:46Z | |
dc.date.available | 2020-05-26T00:10:11Z | |
dc.date.available | 2022-09-22T15:00:46Z | |
dc.date.created | 2020-05-26T00:10:11Z | |
dc.identifier | 03406717 | |
dc.identifier | 14321203 | |
dc.identifier | https://repository.urosario.edu.co/handle/10336/24215 | |
dc.identifier | https://doi.org/10.1007/s00439-019-02066-w | |
dc.identifier.uri | http://repositorioslatinoamericanos.uchile.cl/handle/2250/3444205 | |
dc.description.abstract | Stevens–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. | |
dc.language | eng | |
dc.publisher | Springer | |
dc.relation | Human Genetics, ISSN:03406717, 14321203, Vol.138, No.44176 (2019); pp. 1267-1274 | |
dc.relation | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85074025514&doi=10.1007%2fs00439-019-02066-w&partnerID=40&md5=1b915c3775dff3aa10c0cb5a8493e13b | |
dc.relation | 1274 | |
dc.relation | No. 44176 | |
dc.relation | 1267 | |
dc.relation | Human Genetics | |
dc.relation | Vol. 138 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.rights | Abierto (Texto Completo) | |
dc.source | instname:Universidad del Rosario | |
dc.source | reponame:Repositorio Institucional EdocUR | |
dc.title | Mutant GNLY is linked to Stevens–Johnson syndrome and toxic epidermal necrolysis | |
dc.type | article | |