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.
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
Figures
Figure Gallery
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes