Mutations in human cause limb and cardiac malformation in Holt-Oram syndrome

Craig T. Basson, David R. Bachinsky, Robert C. Lin, Tatjana Levi, Jacob A. Elkins, Johann Soults, David Grayzel, Elena Kroumpouzou, Thomas A. Traill, Janine Leblanc-Straceski, Beatrice Renault, Raju Kucherlapati, J. G. Seidman, Christine E. Seidman

Research output: Contribution to journalReview articlepeer-review

853 Scopus citations


Holt-Oram syndrome is characterized by upper limb malformations and cardiac septation defects. Here, we demonstrate that mutations in the human TBX5 gene underlie this disorder. TBX5 was cloned from the disease locus on human chromosome 12q24.1 and identified as a member of the T-box transcription factor family. A nonsense mutation in TBX5 causes Holt-Oram syndrome in affected members of one family; a TBX5 missense mutation was identified in affected members of another. We conclude that TBX5 is critical for limb and heart development and suggest that haploinsufficiency of TBX5 causes Holt-Oram syndrome.

Original languageEnglish (US)
Pages (from-to)30-35
Number of pages6
JournalNature genetics
Issue number1
StatePublished - Jan 1997

ASJC Scopus subject areas

  • Genetics


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