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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Johnson, DW; Berg, JN; Baldwin, MA; Gallione, CJ; Marondel, I; Yoon, SJ; Stenzel, TT; Speer, M; Pericak-Vance, MA; Diamond, A; Guttmacher, AE; Jackson, CE; Attisano, L; Kucherlapati, R; Porteous, ME; Marchuk, DA

Published Date

  • June 1996

Published In

Volume / Issue

  • 13 / 2

Start / End Page

  • 189 - 195

PubMed ID

  • 8640225

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng0696-189


  • eng

Conference Location

  • United States