Am J Hum Genet
| Autor: | Kelly Springell, Carmel Toomes, Sigmar Stricker, Jacquelyn Bond, Lihadh Al-Gazali, James J. Cox, G. Karbani, Sheila Scott, Rowena Stern, Saghira Malik Sharif, Stefan Mundlos, Emma Roberts, Dhavendra Kumar, Petra Seemann, E. Sherridan, Christopher Geoffrey Woods |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Limb Buds Ectromelia Genetic Linkage Molecular Sequence Data Mutation Missense Schinzel phocomelia syndrome Phocomelia Biology Avian Proteins Organ Culture Techniques Proto-Oncogene Proteins Report medicine Genetics Animals Humans Missense mutation Limb development Genetics(clinical) Amino Acid Sequence Genetics (clinical) Aplasia medicine.disease Hypoplasia Pedigree Radiography Wnt Proteins WNT7A Female Chickens Chondrogenesis Gene Deletion |
| Zdroj: | American Journal of Human Genetics (Chicago, IL) |
| ISSN: | 0002-9297 |
| DOI: | 10.1086/506332 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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