Novel mutations and polymorphisms in genes causing hereditary hemorrhagic telangiectasia

Hum Mutat. 2005 Mar;25(3):320-1. doi: 10.1002/humu.9312.


Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular disorder caused by mutations in Endoglin (ENG) or activin receptor-like kinase-1 (ALK1, ACVRL1) genes. We performed molecular characterization in clinically affected probands of 31 HHT families and detected a total of 28 different mutations in the two genes, including four shared by more than one family. Twelve mutations were identified in the ENG gene, six of which were novel and comprised two nonsense mutations in exons 6 and 8, deletions in exons 5 and 11, and splice site mutations in exon 12 and intron 8. Eleven of sixteen mutations identified in the ALK1 gene were novel single base pair substitutions in exons 4, 7, 8, and 9. We also describe the first de novo ALK1 mutation that causes a previously unreported c.1133C>A substitution of a highly conserved residue (p.P378H). The proband and his two daughters, who also carried the familial mutation, all suffered from gastrointestinal (GI) bleeding. In addition, we report seven newly identified polymorphisms and summarize all known ones in both genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors, Type II
  • Adolescent
  • Adult
  • Amino Acid Substitution
  • Antigens, CD / genetics*
  • DNA Mutational Analysis
  • Endoglin
  • Exons / genetics
  • Female
  • Gastrointestinal Hemorrhage / etiology
  • Humans
  • Intracranial Arteriovenous Malformations / etiology
  • Introns / genetics
  • Liver / pathology
  • Lung / pathology
  • Male
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation, Missense*
  • Point Mutation*
  • Polymorphism, Single Nucleotide*
  • RNA Splice Sites / genetics
  • Receptors, Cell Surface / genetics*
  • Telangiectasia, Hereditary Hemorrhagic / complications
  • Telangiectasia, Hereditary Hemorrhagic / genetics*
  • Telangiectasia, Hereditary Hemorrhagic / pathology


  • Antigens, CD
  • ENG protein, human
  • Endoglin
  • Membrane Proteins
  • RNA Splice Sites
  • Receptors, Cell Surface
  • ACVRL1 protein, human
  • Activin Receptors, Type II