Mutation analysis of a family with hereditary hemorrhagic telangiectasia associated with hepatic arteriovenous malformation

J Formos Med Assoc. 2001 Dec;100(12):817-9.


Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by multisystemic vascular dysplasia. Two related genes, endoglin and activin receptor-like kinase (ALK-1), have been mapped to chromosomes 9q34 and 12q13, respectively. We describe a Taiwanese HHT family with hepatic arteriovenous malformation. Clinical and molecular evaluations were performed in eight members of this family, and HHT symptoms were found in three adults. Short tandem repeat markers were used to perform linkage analysis, and this family was classified as HHT type 2 (ALK-1 gene). The exons of ALK-1 were amplified using the polymerase chain reaction and subjected to direct DNA sequencing. The mutation causing the disease was located at ALK-1 codon 411, causing an arginine to glutamine substitution. Five members of this family carried the mutated ALK-1 gene. This investigation successfully used linkage and sequencing techniques to perform molecular diagnosis of HHT.

Publication types

  • Case Reports

MeSH terms

  • Activin Receptors, Type I / genetics*
  • Activin Receptors, Type II
  • Aged
  • Amino Acid Substitution
  • Antigens, CD
  • Arteriovenous Malformations / complications*
  • Arteriovenous Malformations / genetics
  • Chromosome Mapping*
  • Chromosomes, Human, Pair 12
  • Chromosomes, Human, Pair 9
  • Endoglin
  • Hepatic Artery / abnormalities*
  • Hepatic Veins / abnormalities*
  • Humans
  • Male
  • Mutation, Missense*
  • Pedigree
  • Receptors, Cell Surface
  • Telangiectasia, Hereditary Hemorrhagic / complications
  • Telangiectasia, Hereditary Hemorrhagic / genetics*
  • Vascular Cell Adhesion Molecule-1 / genetics*


  • Antigens, CD
  • ENG protein, human
  • Endoglin
  • Receptors, Cell Surface
  • Vascular Cell Adhesion Molecule-1
  • ACVRL1 protein, human
  • Activin Receptors, Type I
  • Activin Receptors, Type II