Mutations in human TBX5 [corrected] cause limb and cardiac malformation in Holt-Oram syndrome

Nat Genet. 1997 Jan;15(1):30-5. doi: 10.1038/ng0197-30.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abnormalities, Multiple / embryology
  • Abnormalities, Multiple / genetics*
  • Amino Acid Sequence
  • Animals
  • Arm / abnormalities*
  • Arm / embryology
  • Base Sequence
  • Chromosomes, Human, Pair 12
  • Cloning, Molecular
  • DNA
  • DNA Mutational Analysis
  • Heart Defects, Congenital / embryology
  • Heart Defects, Congenital / genetics*
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • Sequence Homology, Amino Acid
  • Syndrome
  • T-Box Domain Proteins*
  • Transcription Factors / genetics*


  • T-Box Domain Proteins
  • T-box transcription factor 5
  • Transcription Factors
  • DNA

Associated data

  • GENBANK/U80987