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Abstract

Holt-Oram syndrome is a developmental disorder affecting the heart and upper limb, the gene for which was mapped to chromosome 12 two years ago. We have now identified a gene for this disorder (HOS1). The gene (TBX5) is a member of the Brachyury (T) family corresponding to the mouse TbxS gene. We have identified six mutations, three in HOS families and three in sporadic HOS cases. Each of the mutations introduces a premature stop codon in the TBXS gene product. Tissue in situ hybridization studies on human embryos from days 26 to 52 of gestation reveal expression of TBXS in heart and limb, consistent with a role in human embryonic development.

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Author notes

    • Jonathan A. Terrett

    Present address: Smithkline Beecham Pharmaceuticals, Essex, UK

    • Alan J. Buckler

    Present address: Sequana Therapeutics, Lajolla, California, USA

Affiliations

  1. Department of Genetics, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK

    • Quan Yi Li
    • , Ruth A. Newbury-Ecob
    • , Jonathan A. Terrett
    • , Cheong Ho Yi
    •  & J. David Brook
  2. Centre for Medical Genetics, City Hospital NHS Trust, University ofNottingham, Nottingham, NG51PB, UK

    • Quan Yi Li
    • , Ruth A. Newbury-Ecob
    • , Jonathan A. Terrett
    • , Cheong Ho Yi
    • , Ian D. Young
    • , J. Alexander Raeburn
    •  & J. David Brook
  3. Department of Clinical Genetics, Royal Hospital for Sick Children, Bristol, BS2 8JJ, UK

    • Ruth A. Newbury-Ecob
  4. Department of Human Genetics and University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4AA, UK

    • David I. Wilson
    • , Andrew R.J. Curtis
    • , Philip J. Bullen
    •  & Tom Strachan
  5. Department of Human Genetics, University of Michigan, Ann Harbor, Michigan, 48109-0674, USA

    • Tom Gebuhr
    •  & David J. Law
  6. Department of Fetal Medicine, University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4AA, UK

    • Philip J. Bullen
    •  & Stephen C. Robson
  7. Departement de Pediatrie, INSERM U-393, Hopital des Enfants-Malades, 75743, Paris, France

    • Damien Bonnet
    •  & Stanislas Lyonnet
  8. Department of Neurogenetics, Massachusetts General Hospital, Charlestown, Massachusetts, USA

    • Alan J. Buckler

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https://doi.org/10.1038/ng0197-21

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