PUBLICATION
WNT5A mutations in patients with autosomal dominant Robinow syndrome
- Authors
- Person, A.D., Beiraghi, S., Sieben, C.M., Hermanson, S., Neumann, A.N., Robu, M.E., Schleiffarth, J.R., Billington, C.J. Jr, van Bokhoven, H., Hoogeboom, J.M., Mazzeu, J.F., Petryk, A., Schimmenti, L.A., Brunner, H.G., Ekker, S.C., and Lohr, J.L.
- ID
- ZDB-PUB-091120-63
- Date
- 2010
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists 239(1): 327-337 (Journal)
- Registered Authors
- Ekker, Stephen C., Hermanson, Spencer, Petryk, Anna
- Keywords
- Wnt5a, Ror2, Robinow syndrome
- MeSH Terms
-
- Abnormalities, Multiple/genetics*
- Amino Acid Sequence
- Animals
- Bone Diseases, Developmental/genetics*
- Chromosome Mapping
- Crosses, Genetic
- DNA Primers/genetics
- Embryonic Development/genetics*
- Genes, Dominant/genetics
- Humans
- In Situ Hybridization
- Mice
- Molecular Sequence Data
- Mutation, Missense/genetics*
- Proto-Oncogene Proteins/genetics*
- Proto-Oncogene Proteins/metabolism
- Receptor Tyrosine Kinase-like Orphan Receptors/genetics
- Receptor Tyrosine Kinase-like Orphan Receptors/metabolism
- Signal Transduction/genetics*
- Syndrome
- Wnt Proteins/genetics*
- Wnt Proteins/metabolism
- Xenopus
- Zebrafish
- PubMed
- 19918918 Full text @ Dev. Dyn.
Citation
Person, A.D., Beiraghi, S., Sieben, C.M., Hermanson, S., Neumann, A.N., Robu, M.E., Schleiffarth, J.R., Billington, C.J. Jr, van Bokhoven, H., Hoogeboom, J.M., Mazzeu, J.F., Petryk, A., Schimmenti, L.A., Brunner, H.G., Ekker, S.C., and Lohr, J.L. (2010) WNT5A mutations in patients with autosomal dominant Robinow syndrome. Developmental Dynamics : an official publication of the American Association of Anatomists. 239(1):327-337.
Abstract
Robinow syndrome is a skeletal dysplasia with both autosomal dominant and autosomal recessive inheritance patterns. It is characterized by short stature, limb shortening, genital hypoplasia, and craniofacial abnormalities. The etiology of dominant Robinow syndrome is unknown; however, the phenotypically more severe autosomal recessive form of Robinow syndrome has been associated with mutations in the orphan tyrosine kinase receptor, ROR2, which has recently been identified as a putative WNT5A receptor. Here, we show that two different missense mutations in WNT5A, which result in amino acid substitutions of highly conserved cysteines, are associated with autosomal dominant Robinow syndrome. One mutation has been found in all living affected members of the original family described by Meinhard Robinow and another in a second unrelated patient. These missense mutations result in decreased WNT5A activity in functional assays of zebrafish and Xenopus development. This work suggests that a WNT5A/ROR2 signal transduction pathway is important in human craniofacial and skeletal development and that proper formation and growth of these structures is sensitive to variations in WNT5A function.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping