Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/208021
New genetic drivers in hemorrhagic hereditary telangiectasia.
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disease inherited in an autosomal dominant manner. Disease-causing variants in endoglin (ENG) and activin A receptor type II-like 1 (ACVRL1) genes are detected in around 90% of the patients; also 2% of patients harbor pathogenic variants at SMAD4 and GDF2. Importantly, the genetic cause of 8% of patients with clinical HHT remains unknown. Here, we present new putative genetic drivers of HHT. Methods: To identify new HHT genetic drivers, we performed exome sequencing of 19 HHT patients and relatives with unknown HHT genetic etiology. We applied a multistep filtration strategy to catalog deleterious variants and prioritize gene candidates based on their known relevance in endothelial cell biology. Additionally, we performed in vitro validation of one of the identified variants. Results: We identified variants in the INHA, HIF1A, JAK2, DNM2, POSTN, ANGPTL4, FOXO1 and SMAD6 genes as putative drivers in HHT. We have identified the SMAD6 p.(Glu407Lys) variant in one of the families; this is a loss-of-function variant leading to the activation of the BMP/TGFβ signaling in endothelial cells. Conclusions: Variants in these genes should be considered for genetic testing in patients with HHT phenotype and negative for ACVRL1/ENG mutations.
Matèries
Matèries (anglès)
Citació
Citació
CERDÀ, Pau, CASTILLO, Sandra d., AGUILERA, Cinthia, IRIARTE, Adriana, ROCAMORA, José luis, LARRINAGA, Ane m., VIÑALS CANALS, Francesc, GRAUPERA I GARCIA-MILÀ, Mariona, RIERA MESTRE, Antoni. New genetic drivers in hemorrhagic hereditary telangiectasia. . _European Journal Of Internal Medicine_. 2024. Vol. 119, núm. 99-108. [consulta: 24 de gener de 2026]. ISSN: 0953-6205. [Disponible a: https://hdl.handle.net/2445/208021]