A Gain-of-Function Mutation in TRPA1 Causes familial episodic pain syndrome

dc.creatorPineda Trujillo, Nicolás Guillermo
dc.creatorBedoya Berrío, Gabriel de Jesús
dc.creatorRuiz Linares, Andrés
dc.creatorKremeyer, Barbara
dc.creatorLopera Restrepo, Francisco Javier
dc.creatorCox, James J.
dc.creatorMomin, Aliakmal
dc.creatorRugiero, Francois
dc.creatorMarsh, Steve
dc.creatorWoods, C. Geoffrey
dc.creatorJones, Nicholas G.
dc.creatorPaterson, Kathryn J.
dc.creatorFricker, Florence R.
dc.creatorVillegas Lanau, Carlos Andrés
dc.creatorAcosta Baena, Natalia
dc.creatorRamírez, Juan Diego
dc.creatorZea, Julián
dc.creatorBurley, Mari Wyn
dc.creatorBennett, David L.H.
dc.creatorWood, John N.
dc.date2023-03-12T19:25:34Z
dc.date2023-03-12T19:25:34Z
dc.date2010
dc.date.accessioned2024-04-23T14:17:34Z
dc.date.available2024-04-23T14:17:34Z
dc.identifierKremeyer B, Lopera F, Cox JJ, Momin A, Rugiero F, Marsh S, Woods CG, Jones NG, Paterson KJ, Fricker FR, Villegas A, Acosta N, Pineda-Trujillo NG, Ramírez JD, Zea J, Burley MW, Bedoya G, Bennett DL, Wood JN, Ruiz-Linares A. A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome. Neuron. 2010 Jun 10;66(5):671-80. doi: 10.1016/j.neuron.2010.04.030.
dc.identifier0896-6273
dc.identifierhttps://hdl.handle.net/10495/33938
dc.identifier10.1016/j.neuron.2010.04.030
dc.identifier1097-4199
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/9229443
dc.descriptionABSTRACT: Human monogenic pain syndromes have provided important insights into the molecular mechanisms that underlie normal and pathological pain states. We describe an autosomal-dominant familial episodic pain syndrome characterized by episodes of debilitating upper body pain, triggered by fasting and physical stress. Linkage and haplotype analysis mapped this phenotype to a 25 cM region on chromosome 8q12–8q13. Candidate gene sequencing identified a point mutation (N855S) in the S4 transmembrane segment of TRPA1, a key sensor for environmental irritants. The mutant channel showed a normal pharmacological profile but altered biophysical properties, with a 5-fold increase in inward current on activation at normal resting potentials. Quantitative sensory testing demonstrated normal baseline sensory thresholds but an enhanced secondary hyperalgesia to punctate stimuli on treatment with mustard oil. TRPA1 antagonists inhibit the mutant channel, promising a useful therapy for this disorder. Our findings provide evidence that variation in the TRPA1 gene can alter pain perception in humans.
dc.descriptionCOL0006723
dc.descriptionCOL0010744
dc.format10
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.languageeng
dc.publisherCell Press
dc.publisherGenética Molecular (GENMOL)
dc.publisherGrupo de Neurociencias de Antioquia
dc.publisherCambridge, Estados Unidos
dc.relationNeuron
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.5/co/
dc.rightshttp://purl.org/coar/access_right/c_abf2
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAnálisis de Secuencia de Proteína
dc.subjectAmino Acid Sequence
dc.subjectCanales de Calcio - genética
dc.subjectCalcium Channels - genetics
dc.subjectLínea Celular
dc.subjectCell Line
dc.subjectDatos de Secuencia Molecular
dc.subjectMolecular Sequence Data
dc.subjectProteínas del Tejido Nervioso - genética
dc.subjectNerve Tissue Proteins - genetics
dc.subjectDolor - genética
dc.subjectPain - genetics
dc.subjectDolor - fisiopatología
dc.subjectPain - physiopathology
dc.subjectDimensión del Dolor - métodos
dc.subjectPain Measurement - methods
dc.subjectMutación Puntual
dc.subjectPoint Mutation
dc.subjectCanal Catiónico TRPA1
dc.subjectTRPA1 Cation Channel
dc.subjectCanales de Potencial de Receptor Transitorio
dc.subjectTransient Receptor Potential Channels
dc.titleA Gain-of-Function Mutation in TRPA1 Causes familial episodic pain syndrome
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.typehttp://purl.org/coar/resource_type/c_2df8fbb1
dc.typehttps://purl.org/redcol/resource_type/ART
dc.typeArtículo de investigación


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