Overlapping upstream ORFs ending at c.125 lead to reduced Endoglin, contributing to Hereditary Hemorrhagic Telangiectasia
| dc.rights.license | open | en_US |
| hal.structure.identifier | Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases | |
| dc.contributor.author | SOUKARIEH, Omar | |
| hal.structure.identifier | Institut National de la Santé et de la Recherche Médicale [INSERM] | |
| hal.structure.identifier | Université de Bordeaux [UB] | |
| dc.contributor.author | PROUST, Carole | |
| hal.structure.identifier | Institut National de la Santé et de la Recherche Médicale [INSERM] | |
| hal.structure.identifier | Université de Bordeaux [UB] | |
| dc.contributor.author | DEIBER, Clémence | |
| hal.structure.identifier | Institut National de la Santé et de la Recherche Médicale [INSERM] | |
| hal.structure.identifier | Université de Bordeaux [UB] | |
| dc.contributor.author | MEGUERDITCHIAN, Caroline | |
| hal.structure.identifier | Hospices Civils de Lyon [HCL] | |
| dc.contributor.author | GUILHEM, Alexandre | |
| dc.contributor.author | MOHAMED, Shirine | |
| hal.structure.identifier | UFR Sciences de la santé Simone Veil [UVSQ Santé] | |
| dc.contributor.author | GOYENVALLE, Aurelie | |
| dc.contributor.author | JASPARD-VINASSA, Beatrice | |
| hal.structure.identifier | Hospices Civils de Lyon [HCL] | |
| dc.contributor.author | DUPUIS-GIROD, Sophie | |
| hal.structure.identifier | Institut National de la Santé et de la Recherche Médicale [INSERM] | |
| dc.contributor.author | TRÉGOUËT, David-Alexandre | |
| dc.date.accessioned | 2025-07-08T08:29:39Z | |
| dc.date.available | 2025-07-08T08:29:39Z | |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/207256 | |
| dc.description.abstractEn | Hereditary 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.sponsorship | Etude 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-CE17-0042 | en_US |
| dc.description.sponsorship | Vaincre les maladies vasculaires cérébrales par un nouveau paradigme de prévention de précision et d'innovation thérapeutique - ANR-23-IAHU-0001 | en_US |
| dc.language.iso | EN | en_US |
| dc.subject.en | ORFS | |
| dc.subject.en | Lead (geology) | |
| dc.title.en | Overlapping upstream ORFs ending at c.125 lead to reduced Endoglin, contributing to Hereditary Hemorrhagic Telangiectasia | |
| dc.type | Document de travail - Pré-publication | en_US |
| dc.identifier.doi | 10.21203/rs.3.rs-4808835/v1 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio] | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Médecine humaine et pathologie | en_US |
| bordeaux.hal.laboratories | Biologie des maladies cardiovasculaires (BMC) - UMR 1034 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | INSERM | en_US |
| bordeaux.import.source | hal | |
| hal.identifier | hal-05059184 | |
| hal.version | 1 | |
| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | false | |
| workflow.import.source | hal | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.subtype | Prepublication/Preprint | en_US |
| bordeaux.COinS | ctx_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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