WNT5A Mutations in Patients With Autosomal Dominant Robinow Syndrome

Autor: J. Robert Schleiffarth, Spencer Hermanson, Jeannette A.M. Hoogeboom, Anna Petryk, Christine M. Sieben, Ann N. Neumann, Anthony D. Person, Mara E. Robu, Han G. Brunner, Soraya Beiraghi, Hans van Bokhoven, Lisa A. Schimmenti, Stephen C. Ekker, Jamie L. Lohr, Juliana F. Mazzeu, Charles J. Billington
Přispěvatelé: Clinical Genetics
Rok vydání: 2010
Předmět:
Genetics and epigenetic pathways of disease [NCMLS 6]
Xenopus
Molecular Sequence Data
Mutation
Missense
Receptor tyrosine kinase-like orphan receptor
Embryonic Development
Biology
medicine.disease_cause
Receptor Tyrosine Kinase-like Orphan Receptors
Short stature
Receptor tyrosine kinase
Wnt-5a Protein
Article
Genomic disorders and inherited multi-system disorders [IGMD 3]
Mice
Proto-Oncogene Proteins
medicine
Missense mutation
Animals
Humans
Abnormalities
Multiple
Amino Acid Sequence
Craniofacial
Crosses
Genetic
In Situ Hybridization
Zebrafish
DNA Primers
Genes
Dominant
Genetics
Mutation
Bone Diseases
Developmental
Chromosome Mapping
ROR2
Syndrome
medicine.disease
Molecular biology
Robinow syndrome
Wnt Proteins
body regions
embryonic structures
biology.protein
sense organs
medicine.symptom
Functional Neurogenomics [DCN 2]
Developmental Biology
Signal Transduction
Zdroj: Developmental Dynamics, 239(1), 327-337. Wiley-Liss Inc.
Developmental Dynamics, 239, 327-37
Developmental Dynamics, 239, 1, pp. 327-37
ISSN: 1058-8388
Popis: Contains fulltext : 87463.pdf (Publisher’s version ) (Closed access) 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. 01 januari 2010
Databáze: OpenAIRE
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