PROUST, Carole; DEIBER, Clémence; MEGUERDITCHIAN, Caroline; TUSSEAU, Maud; GUILHEM, Alexandre; MOHAMED, Shirine; GOYENVALLE, Aurélie; JASPARD-VINASSA, Béatrice; DUPUIS-GIROD, Sophie; TRÉGOUËT, David-Alexandre; SOUKARIEH, Omar

doi:10.1038/s42003-025-08461-6

PROUST, Carole
Bordeaux population health [BPH]

DEIBER, Clémence
Bordeaux population health [BPH]

MEGUERDITCHIAN, Caroline
Bordeaux population health [BPH]

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Article de revue

Ce document a été publié dans

Communications Biology. 2025-07-18, vol. 8, n° 1, p. 1072

Résumé en anglais

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. Interestingly, we found that 85% of uAUG-c.125 variants alter the protein levels. Furthermore, we identified 2 variants creating uAUG-c.125 and uCUG-c.125 in HHT patients and experimentally demonstrated their association with reduced endoglin levelsThis 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.< Réduire

Mots clés en anglais

Endoglin

Telangiectasia

Hereditary Hemorrhagic

Humans

Open Reading Frames

5' Untranslated Regions

Polymorphism

Single Nucleotide

Mutation

Male

URI

https://oskar-bordeaux.fr/handle/20.500.12278/207535

DOI

http://dx.doi.org/10.1038/s42003-025-08461-6

Unités de recherche

Biologie des maladies cardiovasculaires (BMC) - UMR 1034

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

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Résumé en anglais

Mots clés en anglais

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