English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/45419
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

5'UTR mutations of ENG cause Hereditary Hemorrhagic Telangiectasia

AuthorsDamjanovich, Kristy; Langa, Carmen ; Blanco, Francisco J. ; McDonald, Jamie; Botella, Luisa María ; Bernabéu, Carmelo ; Wooderchak-Donahue, Whitney; Stevenson, David A.; Bayrak-Toydemir, Pinar
Issue Date22-Dec-2011
PublisherBioMed Central
CitationOrphanet Journal of Rare Diseases. 22, 6(1):85 (2011)
AbstractAbstract Background Hereditary hemorrhagic telangiectasia (HHT) is a vascular disorder characterized by epistaxis, arteriovenous malformations, and telangiectases. The majority of the patients have a mutation in the coding region of the activin A receptor type II-like 1 (ACVRL1) or Endoglin (ENG) gene. However, in approximately 15% of cases, sequencing analysis and deletion/duplication testing fail to identify mutations in the coding regions of these genes. Knowing its vital role in transcription and translation control, we were prompted to investigate the 5'untranslated region (UTR) of ENG. Methods and Results We sequenced the 5'UTR of ENG for 154 HHT patients without mutations in ENG or ACVRL1 coding regions. We found a mutation (c.-127C > T), which is predicted to affect translation initiation and alter the reading frame of endoglin. This mutation was found in a family with linkage to the ENG, as well as in three other patients, one of which had an affected sibling with the same mutation. In vitro expression studies showed that a construct with the c.-127C > T mutation alters the translation and decreases the level of the endoglin protein. In addition, a c.-9G > A mutation was found in three patients, one of whom was homozygous for this mutation. Expression studies showed decreased protein levels suggesting that the c.-9G > A is a hypomorphic mutation. Conclusions Our results emphasize the need for the inclusion of the 5'UTR region of ENG in clinical testing for HHT.
Publisher version (URL)http://dx.doi.org/10.1186/1750-1172-6-85
URIhttp://hdl.handle.net/10261/45419
DOIhttp://dx.doi.org/10.1186/1750-1172-6-85
Appears in Collections:(CIB) Artículos
Files in This Item:
File Description SizeFormat 
1750-1172-6-85.xml77,27 kBXMLView/Open
1750-1172-6-85-S1.TIFF54,5 kBTIFFThumbnail
View/Open
1750-1172-6-85.pdf608,03 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.