Mutations in WNT7A cause a range of limb malformations, including Fuhrmann syndrome and Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome

Am J Hum Genet. 2006 Aug;79(2):402-8. doi: 10.1086/506332. Epub 2006 Jun 23.


Fuhrmann syndrome and the Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome are considered to be distinct limb-malformation disorders characterized by various degrees of limb aplasia/hypoplasia and joint dysplasia in humans. In families with these syndromes, we found homozygous missense mutations in the dorsoventral-patterning gene WNT7A and confirmed their functional significance in retroviral-mediated transfection of chicken mesenchyme cell cultures and developing limbs. The results suggest that a partial loss of WNT7A function causes Fuhrmann syndrome (and a phenotype similar to mouse Wnt7a knockout), whereas the more-severe limb truncation phenotypes observed in Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome result from null mutations (and cause a phenotype similar to mouse Shh knockout). These findings illustrate the specific and conserved importance of WNT7A in multiple aspects of vertebrate limb development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Avian Proteins / genetics
  • Chickens
  • Chondrogenesis / genetics
  • Chondrogenesis / physiology
  • Ectromelia / diagnostic imaging
  • Ectromelia / genetics*
  • Ectromelia / physiopathology
  • Female
  • Gene Deletion
  • Genetic Linkage
  • Humans
  • Limb Buds / growth & development
  • Limb Buds / metabolism
  • Male
  • Molecular Sequence Data
  • Mutation, Missense*
  • Organ Culture Techniques
  • Pedigree
  • Proto-Oncogene Proteins / genetics*
  • Radiography
  • Wnt Proteins / genetics*


  • Avian Proteins
  • Proto-Oncogene Proteins
  • WNT7A protein, Gallus gallus
  • WNT7A protein, human
  • Wnt Proteins