Detection of a significant association between mutations in the ACVRL1 gene and hepatic involvement in German patients with hereditary haemorrhagic telangiectasia

Clin Genet. 2008 Aug;74(2):171-7. doi: 10.1111/j.1399-0004.2008.01029.x. Epub 2008 May 21.


Hereditary haemorrhagic telangiectasia (HHT) is a heterogeneous multisystemic dysplasia of the vascular tissue. This autosomal dominant inherited disorder shows a wide variation in its phenotypic expression. Between 8 and 78% of the HHT patients show arteriovenous malformations of the liver. The molecular basis for hepatic manifestation is still unknown. Two genes are known to play a major role in the development of HHT: activin A receptor type II-like 1 gene (ACVRL1) and ENG. Previously, we and others showed that hepatic involvement is associated with mutations in the ACVRL1 gene, but rarely caused by ENG mutations. Here, we report about the sequencing analysis of a new cohort of 18 adult HHT patients. In these patients, we identified eight novel (four in ACVRL1 and four in ENG) and eight already known mutations. Statistical analysis of our entire data revealed significant differences in the distribution of ACVRL1 and ENG mutations among HHT patients with and without liver involvement (p = 0.0016). The positive predictive value for type 2 HHT (ACVRL1 positive) patients to develop liver disease until the age of 52 years is 68.4%. We conclude that molecular genetic testing of HHT patients is important for prognosis with respect to liver disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors, Type II / genetics*
  • Adolescent
  • Adult
  • Antigens, CD / genetics*
  • Arteriovenous Malformations / genetics
  • Cohort Studies
  • DNA Mutational Analysis
  • Endoglin
  • Female
  • Genetic Testing
  • Germany
  • Humans
  • Liver Circulation / genetics
  • Liver Diseases / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • Receptors, Cell Surface / genetics*
  • Telangiectasia, Hereditary Hemorrhagic / complications*
  • Telangiectasia, Hereditary Hemorrhagic / genetics*


  • Antigens, CD
  • ENG protein, human
  • Endoglin
  • Receptors, Cell Surface
  • ACVRL1 protein, human
  • Activin Receptors, Type II