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Classification of PTEN germline non-truncating variants: a new approach to interpretation

dc.rights.licenseopenen_US
hal.structure.identifierService de génétique médicale
hal.structure.identifierCentre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
dc.contributor.authorMARGOT, Henri
hal.structure.identifierInstitut Bergonié [Bordeaux]
dc.contributor.authorJONES, Natalie
hal.structure.identifierInstitut Bergonié [Bordeaux]
dc.contributor.authorMATIS, Thibaut
hal.structure.identifierInstitut Bergonié [Bordeaux]
dc.contributor.authorBONNEAU, Dominique
dc.contributor.authorBUSA, Tiffany
dc.contributor.authorBONNET, Françoise
dc.contributor.authorCONRAD, Solene
dc.contributor.authorCRIVELLI, Louise
dc.contributor.authorMONIN, Pauline
dc.contributor.authorFERT-FERRER, Sandra
dc.contributor.authorMORTEMOUSQUE, Isabelle
hal.structure.identifierInstitut Bergonié [Bordeaux]
dc.contributor.authorRAAD, Sabine
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorLACOMBE, Didier
dc.contributor.authorCAUX, Frédéric
hal.structure.identifierInstitut Bergonié [Bordeaux]
hal.structure.identifierBoRdeaux Institute in onCology [Inserm U1312 - BRIC]
dc.contributor.authorSEVENET, Nicolas
hal.structure.identifierInstitut Bergonié [Bordeaux]
dc.contributor.authorBUBIEN, Virginie
hal.structure.identifierInstitut Bergonié [Bordeaux]
hal.structure.identifierDépartement de pathologie
hal.structure.identifierPlateforme de génétique moléculaire des cancers d'Aquitaine
hal.structure.identifierActions for OnCogenesis understanding and Target Identification in ONcology [ACTION]
dc.contributor.authorLONGY, Michel
dc.date.accessioned2025-01-31T15:11:33Z
dc.date.available2025-01-31T15:11:33Z
dc.date.issued2024-10-02
dc.identifier.issn1468-6244en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/204692
dc.description.abstractEnPTEN hamartoma tumour syndrome (PHTS) encompasses distinct syndromes, including Cowden syndrome resulting from pathogenic variants. Missense variants account for 30% of PHTS cases, but their classification remains challenging. To address these difficulties, guidelines were published by the Clinical Genome Resource PTEN Variant Curation Expert Panel. Between 2010 and 2020, the Bergonie Institute reference laboratory identified 76 different non-truncating variants in 166 patients, 17 of which have not previously been reported. Variants were initially classified following the current guidelines. Subsequently, a new classification method was developed based on four main criteria: functional exploration, phenotypic features and familial segregation, in silico modelling, and allelic frequency. This new method of classification is more discriminative and reclassifies 25 variants, including 8 variants of unknown significance. This report proposes a revision of the current variant classification criteria which at present rely on functional tests evaluating only the phosphatase activity of PTEN and apply a particularly stringent clinical PHTS score.The classification of non-truncating variants of is facilitated by taking into consideration protein stability for variants with intact phosphatase activity, clinical and segregation criteria adapted to the phenotypic variability of PHTS and by specifying the allelic frequency of variants in the general population. This novel method of classification remains to be validated in a prospective cohort.
dc.language.isoENen_US
dc.subject.enGenetic Predisposition to Disease
dc.subject.enGenetics
dc.subject.enMedical
dc.subject.enMutation
dc.subject.enMissense
dc.title.enClassification of PTEN germline non-truncating variants: a new approach to interpretation
dc.title.alternativeJ Med Geneten_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1136/jmg-2024-109982en_US
dc.subject.halSciences du Vivant [q-bio]/Génétiqueen_US
dc.identifier.pubmed39358013en_US
bordeaux.journalJournal of Medical Geneticsen_US
bordeaux.page1071-1079en_US
bordeaux.volume61en_US
bordeaux.hal.laboratoriesMaladies Rares : Génétique et Métabolisme (MRGM) - UMR 1211en_US
bordeaux.issue12en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcepubmed
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcepubmed
dc.rights.ccCC BY-NC-NDen_US
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