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A disease locus for hereditary haemorrhagic telangiectasia maps to chromosome 9q33–34

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Abstract

Hereditary,haemorrhagic telangiectasia (HHT), or Osler–Weber–Rendu disease, is an autosomal dominant vascular dysplasia of unknown pathogenesis leading to ‘widespread’ dermal, mucosal and visceral telangiectases and recurrent haemorrhage. We have mapped the HHT gene, by linkage analysis, to markers on 9q33–34 in two large multi–generation families. Haplotype analysis and mapping of recombination breakpoints gives a 4 cM interval between D9S61 and D9S63 as the most likely location of the gene. The closest marker, D9S65, is estimated to be within 1 cM of the gene and shows a combined lod score of 11.41. Two potential candidate genes, COL5A1 and ZNF79, are also located within 9q33–34. These results provide a starting point for the eventual cloning of the HHT gene.

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Author notes

  1. M.T. McDonald and K.A. Papenberg: M.T.M. and K.A.P. contributed equally to this work and should be considered as joint first authors.

Authors and Affiliations

  1. Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, 48109, USA

    M.T. McDonald

  2. Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, 48109, USA

    K.A. Papenberg, F.S. Collins & D.A. Marchuk

  3. Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, 48109, USA

    S. Ghosh, J.L. Vanderstoep & M. Boehnke

  4. Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, 48109, USA

    A.A. Glatfelter, A. Zolotor & D.A. Marchuk

  5. Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, 48109, USA

    F.S. Collins

  6. Department of Human Genome Center, University of Michigan, Ann Arbor, Michigan, 48109, USA

    S. Ghosh, B.B. Biesecker, E.A. Helmbold, D.S. Markel, J.L. Vanderstoep, C.E. Jackson & M. Boehnke

  7. Department of Pediatrics, University of Vermont College of Medicine, Burlington, Vermont, 05405, USA

    W.C. McKinnon & A.E. Guttmacher

  8. Division of Clinical and Molecular Genetics, Henry Ford Hospital, Detroit, Michigan, 48202, USA

    C.E. Jackson

  9. Division of Pulmonary Medicine, Henry Ford Hospital, Detroit, Michigan, 48202, USA

    M. Iannuzzi

  10. National Center for Human Genome Research, Bethesda, Maryland, 20892, USA

    F.S. Collins

  11. Department of Human Genetics, University of Newcastle Upon Tyne, Newcastle Upon Tyne, NE2 4AA, UK

    M.E. Porteous

  12. Clinical Genetics Service, Western General Hospital, Edinburgh, EH4 2XY, UK

    M.E. Porteous

  13. Department of Genetics, Duke University Medical Center, Box 3175, Durham, North Carolina, 27710, USA

    D.A. Marchuk

Authors
  1. M.T. McDonald
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  2. K.A. Papenberg
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  3. S. Ghosh
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  4. A.A. Glatfelter
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  5. B.B. Biesecker
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  6. E.A. Helmbold
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  7. D.S. Markel
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  8. A. Zolotor
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  9. W.C. McKinnon
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  10. J.L. Vanderstoep
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  11. C.E. Jackson
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  12. M. Iannuzzi
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  13. F.S. Collins
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  14. M. Boehnke
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  15. M.E. Porteous
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  16. A.E. Guttmacher
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  17. D.A. Marchuk
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McDonald, M., Papenberg, K., Ghosh, S. et al. A disease locus for hereditary haemorrhagic telangiectasia maps to chromosome 9q33–34. Nat Genet 6, 197–204 (1994). https://doi.org/10.1038/ng0294-197

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  • DOI: https://doi.org/10.1038/ng0294-197

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