Mutations in the ALK-1 gene and the phenotype of hereditary hemorrhagic telangiectasia in two large Danish families

Am J Med Genet. 2001 Feb 1;98(4):298-302. doi: 10.1002/1096-8628(20010201)98:4<298::aid-ajmg1093>;2-k.


Mutations in the ENG gene on chromosome 9 (HHT 1) and in the ALK-1 gene on chromosome 12 (HHT 2) have been reported as causes of hereditary hemorrhagic telangiectasia (HHT). HHT 1 has been correlated with a higher prevalence of pulmonary arteriovenous malformations than HHT 2. Other distinct phenotype-genotype correlations have not been described. The prevalence of HHT in the county of Fyn, Denmark, was 15.6 per 100,000 on January 1, 1995. All living patients and their first-degree relatives were invited to attend a detailed clinical examination and blood was drawn for mutation analysis. In two families mutations were identified in exon 8 of the ALK-1 gene. In family 6 we found a T1193A mutation. In this family a high prevalence of PAVM and severe GI bleeding was documented, while in family 8 with a C1120T mutation no individuals with PAVM were identified and only one patient had a history of severe GI bleeding. No mutations in the endoglin locus were found in either family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors
  • DNA / chemistry
  • DNA / genetics
  • DNA Mutational Analysis
  • Denmark
  • Family Health
  • Female
  • Humans
  • Male
  • Mutation
  • Pedigree
  • Phenotype
  • Protein Serine-Threonine Kinases / genetics*
  • Telangiectasia, Hereditary Hemorrhagic / genetics*
  • Telangiectasia, Hereditary Hemorrhagic / pathology


  • DNA
  • Protein Serine-Threonine Kinases
  • Activin Receptors