English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/49802
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
Exportar a otros formatos:

Title

Mutation study of Spanish patients with hereditary hemorrhagic telangiectasia and expression analysis of Endoglin and ALK1

AuthorsFernandez-Lopez, Africa ; Sánz-Rodríguez, Francisco; Zarrabeitia, Roberto; Pérez-Molino, Alfonso; Morales, Carmelo; Restrepo, Carlos M.; Ramírez, José Ramón; Coto, Eliecer; Lenato, Gennaro M.; Bernabéu, Carmelo ; Botella, Luisa María
KeywordsENG
ALK1
ACVRL1
HHT
TGF-β
endothelial cells
Issue DateMar-2006
PublisherWiley-Blackwell
CitationHuman Mutation 27(3):295(2006)
AbstractHereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant and age-dependent vascular disorder originated by mutations in Endoglin (ENG) or activin receptor-like kinase-1 (ALK1, ACVRL1) genes. The first large series HHT analysis in Spanish population has identified mutations in 17 unrelated families. Ten different mutations in ALK1 and six in ENG genes were found. Six unrelated families had a mutation in ENG gene, four representing new mutations, p.Y258fs, pV323fs, p.F279fs (c.834_837del CTTC), and p.F279fsdupC. Eleven unrelated families harboured mutations in ALK1; ten were new mutations identified as p.H328P, p.R145fs, p.G68C, p.A377T, p.H297R, p.M376T, p.C36Y, p.H328P, p.T82del and p.R47P. Overall, ALK1 mutations (HHT2) were predominant over ENG mutations (HHT1), in agreement with data reported for other Mediterranean countries (France, Italy), but at variance with Northern Europe or North America. Endoglin expression in HHT1 or HHT2 activated monocytes and blood outgrowth endothelial cells (BOECs) from older patients was well below the theoretical 50% level expected from the HHT1 haploinsufficiency model, suggesting that the pathogenic endoglin haploinsufficiency leading to the HHT phenotype is age-dependent. Interestingly, ALK1 protein levels of HHT BOECs in some missense ALK1 mutants were similar to controls. In vitro expression of these ALK1 constructs suggests that, in addition to the haploinsufficiency model, certain ALK1 mutants may inhibit the function of the wild type allele
Description10 páginas, 2 figuras, 1 tabla -- PAGS nro. 295
Publisher version (URL)http://dx.doi.org/ 10.1002/humu.9413
URIhttp://hdl.handle.net/10261/49802
DOI10.1002/humu.9413
ISSN1059-7794
E-ISSN1098-1004
Appears in Collections:(CIB) Artículos
Files in This Item:
There are no files associated with this item.
Show full item record
Review this work
 

Related articles:


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