Characterization of a family mutation in the 5’ untranslated region of the endoglin gene causative of hereditary hemorrhagic telangiectasia

Lidia Ruiz-Llorente, Jamie McDonald, Whitney Wooderchak-Donahue, Eric Briggs, Mark Chestnutt, Pinar Bayrak-Toydemir, Carmelo Bernabeu

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Hereditary hemorrhagic telangiectasia (HHT) is a vascular disease characterized by nose and gastrointestinal bleeding, telangiectases in skin and mucosa, and arteriovenous malformations in major internal organs. Most patients carry a mutation in the coding region of the endoglin (ENG) or activin A receptor type II-1 (ACVRL1) gene. Nonetheless, in around 15% of patients, sequencing analysis and duplication/deletion tests fail to pinpoint mutations in the coding regions of these genes. In these cases, it has been shown that sequencing of the 5’-untranslated region (5’UTR) of ENG may be useful to identify novel mutations in the ENG non-coding region. Here we report the genetic characterization and functional analysis of the heterozygous mutation c.-142A>T in the 5’UTR region of ENG found in a family with several members affected by HHT. This variant gives rise to a new initiation codon of the protein that involves the change in its open reading frame. Transfection studies in monkey cells using endoglin expression vectors demonstrated that c-142A>T mutation results in a clear reduction in the levels of the endoglin protein. These results support the inclusion of the 5’UTR of ENG in the standard genetic testing for HHT to increase its sensitivity.

Original languageEnglish (US)
Pages (from-to)333-339
Number of pages7
JournalJournal of Human Genetics
Issue number4
Publication statusPublished - Apr 1 2019


ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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