Tags

Type your tag names separated by a space and hit enter

WNT5A mutations in patients with autosomal dominant Robinow syndrome.
Dev Dyn. 2010 Jan; 239(1):327-37.DD

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.

Links

Publisher Full Text
ncbi.nlm.nih.gov
doi.org
PMC Free PDF

Authors+Show Affiliations

Person AD
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota, USA.
Beiraghi S
No affiliation info available
Sieben CM
No affiliation info available
Hermanson S
No affiliation info available
Neumann AN
No affiliation info available
Robu ME
No affiliation info available
Schleiffarth JR
No affiliation info available
Billington CJ
No affiliation info available
van Bokhoven H
No affiliation info available
Hoogeboom JM
No affiliation info available
Mazzeu JF
No affiliation info available
Petryk A
No affiliation info available
Schimmenti LA
No affiliation info available
Brunner HG
No affiliation info available
Ekker SC
No affiliation info available
Lohr JL
No affiliation info available

MeSH

Abnormalities, MultipleAmino Acid SequenceAnimalsBone Diseases, DevelopmentalChromosome MappingCrosses, GeneticDNA PrimersEmbryonic DevelopmentGenes, DominantHumansIn Situ HybridizationMiceMolecular Sequence DataMutation, MissenseProto-Oncogene ProteinsReceptor Tyrosine Kinase-like Orphan ReceptorsSignal TransductionSyndromeWnt ProteinsWnt-5a ProteinXenopusZebrafish

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19918918

Citation

Person, Anthony D., et al. "WNT5A Mutations in Patients With Autosomal Dominant Robinow Syndrome." Developmental Dynamics : an Official Publication of the American Association of Anatomists, vol. 239, no. 1, 2010, pp. 327-37.
Person AD, Beiraghi S, Sieben CM, et al. WNT5A mutations in patients with autosomal dominant Robinow syndrome. Dev Dyn. 2010;239(1):327-37.
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., & 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), 327-37. https://doi.org/10.1002/dvdy.22156
Person AD, et al. WNT5A Mutations in Patients With Autosomal Dominant Robinow Syndrome. Dev Dyn. 2010;239(1):327-37. PubMed PMID: 19918918.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - WNT5A mutations in patients with autosomal dominant Robinow syndrome. AU - Person,Anthony D, AU - Beiraghi,Soraya, AU - Sieben,Christine M, AU - Hermanson,Spencer, AU - Neumann,Ann N, AU - Robu,Mara E, AU - Schleiffarth,J Robert, AU - Billington,Charles J,Jr AU - van Bokhoven,Hans, AU - Hoogeboom,Jeannette M, AU - Mazzeu,Juliana F, AU - Petryk,Anna, AU - Schimmenti,Lisa A, AU - Brunner,Han G, AU - Ekker,Stephen C, AU - Lohr,Jamie L, PY - 2009/11/18/entrez PY - 2009/11/18/pubmed PY - 2010/4/3/medline SP - 327 EP - 37 JF - Developmental dynamics : an official publication of the American Association of Anatomists JO - Dev Dyn VL - 239 IS - 1 N2 - 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. SN - 1097-0177 UR - https://www.unboundmedicine.com/medline/citation/19918918/WNT5A_mutations_in_patients_with_autosomal_dominant_Robinow_syndrome_ L2 - https://doi.org/10.1002/dvdy.22156 DB - PRIME DP - Unbound Medicine ER -