Mutations causing premature termination codons discriminate and generate cellular and clinical variability in HHT

• Published in: Blood Vol. 143; no. 22; pp. 2314 - 2331
• Main Authors: Bernabéu-Herrero, Maria E., Patel, Dilipkumar, Bielowka, Adrianna, Zhu, JiaYi, Jain, Kinshuk, Mackay, Ian S., Chaves Guerrero, Patricia, Emanuelli, Giulia, Jovine, Luca, Noseda, Michela, Marciniak, Stefan J., Aldred, Micheala A., Shovlin, Claire L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.05.2024; The American Society of Hematology
• Subjects: Activin Receptors, Type II - genetics; Codon, Nonsense; Endoglin - genetics; Endoglin - metabolism; Endothelial Cells - metabolism; Endothelial Cells - pathology; Female; Humans; Male; Mutation; Nonsense Mediated mRNA Decay; Smad4 Protein - genetics; Telangiectasia, Hereditary Hemorrhagic - genetics; Telangiectasia, Hereditary Hemorrhagic - pathology; Vascular Biology

•Loss-of-function variants generating premature termination codons associate with bleeds; RNA levels differ between replicate cell cultures.•No PTC-truncated proteins were detected; ENG Q436X (but not R93X) induced cell stress and had pathogenic AlphaMissense readthrough scores. [Display omitted] Fo...