Special Issue Disease Connections
WNT5A mutations in patients with autosomal dominant Robinow syndrome
Version of Record online: 13 NOV 2009
Copyright © 2009 Wiley-Liss, Inc.
Special Issue: Special Issue on WNT Signaling in Development and Disease
Volume 239, Issue 1, pages 327–337, January 2010
How to Cite
Person, A. D., Beiraghi, S., Sieben, C. M., Hermanson, S., Neumann, A. N., Robu, M. E., Schleiffarth, J. R., Billington, C. J., 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. Dev. Dyn., 239: 327–337. doi: 10.1002/dvdy.22156
- Issue online: 15 DEC 2009
- Version of Record online: 13 NOV 2009
- Manuscript Accepted: 20 SEP 2009
- MinnCResT Training Program (NIDCR). Grant Number: T32-DE07288-07
- Musculoskeletal Training Grant NIH-NIAMS. Grant Number: T32 AR050938
- Robinow syndrome
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. Developmental Dynamics 239:327–337, 2010. © 2009 Wiley-Liss, Inc.