Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2

Nat Genet. 1996 Jun;13(2):189-95. doi: 10.1038/ng0696-189.

Abstract

Hereditary haemorrhagic telangiectasia, or Osler-Rendu-Weber (ORW) syndrome, is an autosomal dominant vascular dysplasia. So far, two loci have been demonstrated for ORW. Linkage studies established an ORW locus at chromosome 9q3; endoglin was subsequently identified as the ORW1 gene. A second locus, designated ORW2, was mapped to chromosome 12. Here we report a new 4 cM interval for ORW2 that does not overlap with any previously defined. A 1.38-Mb YAC contig spans the entire interval. It includes the activin receptor like kinase 1 gene (ACVRLK1 or ALK1), a member of the serine-threonine kinase receptor family expressed in endothelium. We report three mutations in the coding sequence of the ALK1 gene in those families which show linkage of the ORW phenotype to chromosome 12. Our data suggest a critical role for ALK1 in the control of blood vessel development or repair.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activin Receptors
  • Amino Acid Sequence
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 12*
  • Female
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Protein-Serine-Threonine Kinases / genetics*
  • Telangiectasia, Hereditary Hemorrhagic / classification
  • Telangiectasia, Hereditary Hemorrhagic / genetics*

Substances

  • Protein-Serine-Threonine Kinases
  • Activin Receptors

Associated data

  • GENBANK/L11695
  • GENBANK/U04692
  • GENBANK/U05209
  • GENBANK/U11442
  • GENBANK/Z22533
  • GENBANK/Z22534
  • GENBANK/Z22535
  • GENBANK/Z22536
  • GENBANK/Z23143