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Overlapping upstream ORFs ending at c.125 lead to reduced Endoglin, contributing to Hereditary Hemorrhagic Telangiectasia

dc.rights.licenseopenen_US
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorSOUKARIEH, Omar
hal.structure.identifierInstitut National de la Santé et de la Recherche Médicale [INSERM]
hal.structure.identifierUniversité de Bordeaux [UB]
dc.contributor.authorPROUST, Carole
hal.structure.identifierInstitut National de la Santé et de la Recherche Médicale [INSERM]
hal.structure.identifierUniversité de Bordeaux [UB]
dc.contributor.authorDEIBER, Clémence
hal.structure.identifierInstitut National de la Santé et de la Recherche Médicale [INSERM]
hal.structure.identifierUniversité de Bordeaux [UB]
dc.contributor.authorMEGUERDITCHIAN, Caroline
hal.structure.identifierHospices Civils de Lyon [HCL]
dc.contributor.authorGUILHEM, Alexandre
dc.contributor.authorMOHAMED, Shirine
hal.structure.identifierUFR Sciences de la santé Simone Veil [UVSQ Santé]
dc.contributor.authorGOYENVALLE, Aurelie
dc.contributor.authorJASPARD-VINASSA, Beatrice
hal.structure.identifierHospices Civils de Lyon [HCL]
dc.contributor.authorDUPUIS-GIROD, Sophie
hal.structure.identifierInstitut National de la Santé et de la Recherche Médicale [INSERM]
dc.contributor.authorTRÉGOUËT, David-Alexandre
dc.date.accessioned2025-07-08T08:29:39Z
dc.date.available2025-07-08T08:29:39Z
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/207256
dc.description.abstractEnHereditary Hemorrhagic Telangiectasia (HHT) is a rare vascular disease mainly caused by pathogenic mutations in ACVRL1 and ENG genes. Despite advances in HHT diagnosis, the molecular origin of some cases remains unclear. Recently, we observed a high prevalence of HHT-causing 5'UTR variants in ENG. These variants commonly introduce upstream AUG codons (uAUGs) at the origin of upstream open reading frames (upORFs) overlapping the coding sequence, all terminating at the same stop codon located at position c.125 (uAUG-c.125). Here, we analyzed all 5'UTR ENG single nucleotide variants that could alter upORFs in silico. Moreover, we found that 85% of uAUG-c.125 variants alter the protein levels. Furthermore, we identified 2 variants creating uAUG and uCUG in HHT patients and experimentally demonstrated their association with reduced endoglin levels This study provides new elements for the interpretation of upORF-altering variants in the 5'UTR of ENG with new insights for the molecular diagnosis of HHT.
dc.description.sponsorshipEtude du caractère pathogène de variants créant des cadres de lecture ouverts en amont de la séquence codante de l'endogline - Nouvelles perspectives thérapeutiques pour la maladie du Rendu-Osler - ANR-23-CE17-0042en_US
dc.description.sponsorshipVaincre les maladies vasculaires cérébrales par un nouveau paradigme de prévention de précision et d'innovation thérapeutique - ANR-23-IAHU-0001en_US
dc.language.isoENen_US
dc.subject.enORFS
dc.subject.enLead (geology)
dc.title.enOverlapping upstream ORFs ending at c.125 lead to reduced Endoglin, contributing to Hereditary Hemorrhagic Telangiectasia
dc.typeDocument de travail - Pré-publicationen_US
dc.identifier.doi10.21203/rs.3.rs-4808835/v1en_US
dc.subject.halSciences du Vivant [q-bio]en_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologieen_US
bordeaux.hal.laboratoriesBiologie des maladies cardiovasculaires (BMC) - UMR 1034en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.import.sourcehal
hal.identifierhal-05059184
hal.version1
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
bordeaux.subtypePrepublication/Preprinten_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.au=SOUKARIEH,%20Omar&PROUST,%20Carole&DEIBER,%20Cl%C3%A9mence&MEGUERDITCHIAN,%20Caroline&GUILHEM,%20Alexandre&rft.genre=preprint


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