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

D. W. Johnson, J. N. Berg, M. A. Baldwin, C. J. Gallione, I. Marondel, S. J. Yoon, T. T. Stenzel, M. Speer, Margaret A Pericak-Vance, A. Diamond, A. E. Guttmacher, C. E. Jackson, L. Attisano, R. Kucherlapati, M. E M Porteous, D. A. Marchuk

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)189-195
Number of pages7
JournalNature Genetics
Volume13
Issue number2
StatePublished - Jun 1 1996
Externally publishedYes

Fingerprint

Activin Receptors
Hereditary Hemorrhagic Telangiectasia
Mutation
Chromosomes, Human, Pair 12
Genes
Blood Vessels
Protein-Serine-Threonine Kinases
Endothelium
Chromosomes
Phenotype

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Johnson, D. W., Berg, J. N., Baldwin, M. A., Gallione, C. J., Marondel, I., Yoon, S. J., ... Marchuk, D. A. (1996). Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type. Nature Genetics, 13(2), 189-195.

Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type. / Johnson, D. W.; Berg, J. N.; Baldwin, M. A.; Gallione, C. J.; Marondel, I.; Yoon, S. J.; Stenzel, T. T.; Speer, M.; Pericak-Vance, Margaret A; Diamond, A.; Guttmacher, A. E.; Jackson, C. E.; Attisano, L.; Kucherlapati, R.; Porteous, M. E M; Marchuk, D. A.

In: Nature Genetics, Vol. 13, No. 2, 01.06.1996, p. 189-195.

Research output: Contribution to journalArticle

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, MEM & Marchuk, DA 1996, 'Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type', Nature Genetics, vol. 13, no. 2, pp. 189-195.
Johnson DW, Berg JN, Baldwin MA, Gallione CJ, Marondel I, Yoon SJ et al. Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type. Nature Genetics. 1996 Jun 1;13(2):189-195.
Johnson, D. W. ; Berg, J. N. ; Baldwin, M. A. ; Gallione, C. J. ; Marondel, I. ; Yoon, S. J. ; Stenzel, T. T. ; Speer, M. ; Pericak-Vance, Margaret A ; Diamond, A. ; Guttmacher, A. E. ; Jackson, C. E. ; Attisano, L. ; Kucherlapati, R. ; Porteous, M. E M ; Marchuk, D. A. / Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type. In: Nature Genetics. 1996 ; Vol. 13, No. 2. pp. 189-195.
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