Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome

Nat Genet. 1997 Jul;16(3):311-5. doi: 10.1038/ng0797-311.


Ulnar-mammary syndrome is a rare pleiotropic disorder affecting limb, apocrine gland, tooth and genital development. We demonstrate that mutations in human TBX3, a member of the T-box gene family, cause ulnar-mammary syndrome in two families. Each mutation (a single nucleotide deletion and a splice-site mutation) is predicted to cause haploinsufficiency of TBX3, implying that critical levels of this transcription factor are required for morphogenesis of several organs. Limb abnormalities of ulnar-mammary syndrome involve posterior elements. Mutations in TBX5, a related and linked gene, cause anterior limb abnormalities in Holt-Oram syndrome. We suggest that during the evolution of TBX3 and TBX5 from a common ancestral gene, each has acquired specific yet complementary roles in patterning the mammalian upper limb.

Publication types

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

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Amino Acid Sequence
  • Apocrine Glands / abnormalities*
  • Arm / abnormalities*
  • Base Sequence
  • Breast / abnormalities
  • Chromosomes, Human, Pair 12
  • DNA Mutational Analysis
  • Female
  • Gene Expression Regulation, Developmental
  • Genitalia / abnormalities*
  • Humans
  • Introns / genetics
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Sequence Alignment
  • Syndrome
  • T-Box Domain Proteins*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*


  • T-Box Domain Proteins
  • T-box transcription factor 5
  • TBX3 protein, human
  • Transcription Factors

Associated data

  • GENBANK/AF002228
  • GENBANK/U28049
  • GENBANK/U80987