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Orphanet Journal of Rare Diseases

, 6:85

First Online: 22 December 2011Received: 18 July 2011Accepted: 22 December 2011


BackgroundHereditary 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 ResultsWe 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.

ConclusionsOur results emphasize the need for the inclusion of the 5-UTR region of ENG in clinical testing for HHT.

Keywords5-UTR region ENG c.-127C > T c.-9G > A homozygous Electronic supplementary materialThe online version of this article doi:10.1186-1750-1172-6-85 contains supplementary material, which is available to authorized users.

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Autor: Kristy Damjanovich - Carmen Langa - Francisco J Blanco - Jamie McDonald - Luisa M Botella - Carmelo Bernabeu - Whitney Wo

Fuente: https://link.springer.com/

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