title: Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2.
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.
authors.affiliation: Department of Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Johnson
authors.forename: J N
authors.initials: JN
authors.lastname: Berg
authors.forename: M A
authors.initials: MA
authors.lastname: Baldwin
authors.forename: C J
authors.initials: CJ
authors.lastname: Gallione
authors.forename: I
authors.initials: I
authors.lastname: Marondel
authors.forename: S J
authors.initials: SJ
authors.lastname: Yoon
authors.forename: T T
authors.initials: TT
authors.lastname: Stenzel
authors.forename: M
authors.initials: M
authors.lastname: Speer
authors.forename: M A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: A
authors.initials: A
authors.lastname: Diamond
authors.forename: A E
authors.initials: AE
authors.lastname: Guttmacher
authors.forename: C E
authors.initials: CE
authors.lastname: Jackson
authors.forename: L
authors.initials: L
authors.lastname: Attisano
authors.forename: R
authors.initials: R
authors.lastname: Kucherlapati
authors.forename: M E
authors.initials: ME
authors.lastname: Porteous
authors.forename: D A
authors.initials: DA
authors.lastname: Marchuk
mesh_terms: D029404:Activin Receptors; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000145:classification / Q000235:genetics*
chemical_list: D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors