Mutant GNLY is linked to Stevens¿Johnson syndrome and toxic epidermal necrolysi

Título traducido de la contribución: GNLY mutante es ligado al sindrome de Stevens Jhonson y necrolisis epidermica toxica

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva


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.
Título traducido de la contribuciónGNLY mutante es ligado al sindrome de Stevens Jhonson y necrolisis epidermica toxica
Idioma originalInglés
Páginas (desde-hasta)1267-1274
Número de páginas7
PublicaciónHuman Genetics
EstadoPublicada - dic 1 2019

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