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

C. G. Woods, S. Stricker, P. Seemann, R. Stern, J. Cox, E. Sherridan, E. Roberts, K. Springell, S. Scott, G. Karbani, S. M. Sharif, C. Toomes, J. Bond, D. Kumar, L. Al-Gazali, S. Mundlos

Research output: Contribution to journalArticlepeer-review

121 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)402-408
Number of pages7
JournalAmerican Journal of Human Genetics
Volume79
Issue number2
DOIs
Publication statusPublished - Aug 2006

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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