English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/180236
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:

Title

Characterization of a mutation in the zona pellucida module of Endoglin that causes Hereditary Hemorrhagic Telangiectasia

AuthorsRuiz-Llorente, Lidia ; Chiapparino, Elisa; Plumitallo, Sara; Danesino, Cesare; Bayrak-Toydemir, Pinar; Pagella, Fabio; Manfredi, Guido; Bernabéu, Carmelo ; Jovine, Luca; Olivieri, Carla
KeywordsENG
HHT
ZP-domain
Issue Date15-May-2019
PublisherElsevier
CitationGene 696:33-39 (2019)
AbstractHereditary hemorrhagic telangiectasia (HHT) is a vascular rare disease characterized by nose and gastrointestinal bleeding, skin and mucosa telangiectasias, and arteriovenous malformations in internal organs. HHT shows an autosomal dominant inheritance and a worldwide prevalence of approximately 1:5000 individuals. In >80% of patients, HHT is caused by mutations in either ENG (HHT1) or ACVRL1 (HHT2) genes, which code for the membrane proteins Endoglin and Activin A Receptor Type II-Like Kinase 1 (ALK1), respectively, both belonging to the TGF-β/BMP signaling pathway. In this work, we describe a novel mutation in exon 9 of ENG (c.1145 G > A) found in five affected members of a family, all of them with characteristic symptoms of HHT. This mutation involves Cys382 residue of the Endoglin protein (p.Cys382 > Tyr) in the zona pellucida (ZP) module of its extracellular region. This is a critical residue involved in a conserved intrachain disulphide bond and in the correct folding of the protein. In fact, transfection studies in human cells using Endoglin expression vectors demonstrated that the p.Cys382 > Tyr mutation results in a marked reduction in the levels of the Endoglin protein. These results demonstrate the pathogenic role for this variant in HHT1 and confirm the key function of Cys382 in Endoglin expression.
Description7 p.-4 fig.
Publisher version (URL)https://doi.org/10.1016/j.gene.2019.02.016
URIhttp://hdl.handle.net/10261/180236
DOIhttp://dx.doi.org/10.1016/j.gene.2019.02.016
ISSN0378-1119
E-ISSN1879-0038
Appears in Collections:(CIB) Artículos
Files in This Item:
File Description SizeFormat 
restringido.pdfRestringido20,59 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.