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De novo WNT5A-associated autosomal dominant Robinow syndrome suggests specificity of genotype and phenotype.
Clin Genet. 2015; 87(1):34-41.CG

Abstract

Robinow Syndrome (RS), a rare skeletal dysplasia syndrome, is characterized by dysmorphic features resembling a fetal face, mesomelic limb shortening, hypoplastic external genitalia in males, and renal and vertebral anomalies. Both autosomal dominant and autosomal recessive patterns of inheritance have been reported. Since the description of autosomal dominant Robinow Syndrome (ADRS; OMIM 180700) in 1969 by Meinhard Robinow and colleagues, the molecular etiology remained elusive until only recently. WNT5A was proposed to be the candidate gene for ADRS, as mutations were found in two affected families, one of those being the originally described index family. We report three families with RS caused by novel heterozygous WNT5A mutations, which were confirmed in the first family by whole exome sequencing, and in all by Sanger sequencing. To our knowledge, this is the largest number of published families with ADRS in whom a WNT5A mutation was identified. Families 1 and 2 are the first cases showing de novo inheritance in the affected family members and thus strengthen the evidence for WNT5A as the causative gene in ADRS. Finally, we propose WNT5A mutation specificity in ADRS, which may affect interactions with other proteins in the Wnt pathway.

Authors+Show Affiliations

The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, Toronto, ON, Canada; Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24716670

Citation

Roifman, M, et al. "De Novo WNT5A-associated Autosomal Dominant Robinow Syndrome Suggests Specificity of Genotype and Phenotype." Clinical Genetics, vol. 87, no. 1, 2015, pp. 34-41.
Roifman M, Marcelis CL, Paton T, et al. De novo WNT5A-associated autosomal dominant Robinow syndrome suggests specificity of genotype and phenotype. Clin Genet. 2015;87(1):34-41.
Roifman, M., Marcelis, C. L., Paton, T., Marshall, C., Silver, R., Lohr, J. L., Yntema, H. G., Venselaar, H., Kayserili, H., van Bon, B., Seaward, G., Brunner, H. G., & Chitayat, D. (2015). De novo WNT5A-associated autosomal dominant Robinow syndrome suggests specificity of genotype and phenotype. Clinical Genetics, 87(1), 34-41. https://doi.org/10.1111/cge.12401
Roifman M, et al. De Novo WNT5A-associated Autosomal Dominant Robinow Syndrome Suggests Specificity of Genotype and Phenotype. Clin Genet. 2015;87(1):34-41. PubMed PMID: 24716670.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - De novo WNT5A-associated autosomal dominant Robinow syndrome suggests specificity of genotype and phenotype. AU - Roifman,M, AU - Marcelis,C L M, AU - Paton,T, AU - Marshall,C, AU - Silver,R, AU - Lohr,J L, AU - Yntema,H G, AU - Venselaar,H, AU - Kayserili,H, AU - van Bon,B, AU - Seaward,G, AU - ,, AU - Brunner,H G, AU - Chitayat,D, Y1 - 2014/05/24/ PY - 2014/01/26/received PY - 2014/03/30/revised PY - 2014/04/07/accepted PY - 2014/4/11/entrez PY - 2014/4/11/pubmed PY - 2015/8/21/medline KW - Robinow syndrome KW - WNT5A KW - autosomal dominant KW - skeletal dysplasia SP - 34 EP - 41 JF - Clinical genetics JO - Clin Genet VL - 87 IS - 1 N2 - Robinow Syndrome (RS), a rare skeletal dysplasia syndrome, is characterized by dysmorphic features resembling a fetal face, mesomelic limb shortening, hypoplastic external genitalia in males, and renal and vertebral anomalies. Both autosomal dominant and autosomal recessive patterns of inheritance have been reported. Since the description of autosomal dominant Robinow Syndrome (ADRS; OMIM 180700) in 1969 by Meinhard Robinow and colleagues, the molecular etiology remained elusive until only recently. WNT5A was proposed to be the candidate gene for ADRS, as mutations were found in two affected families, one of those being the originally described index family. We report three families with RS caused by novel heterozygous WNT5A mutations, which were confirmed in the first family by whole exome sequencing, and in all by Sanger sequencing. To our knowledge, this is the largest number of published families with ADRS in whom a WNT5A mutation was identified. Families 1 and 2 are the first cases showing de novo inheritance in the affected family members and thus strengthen the evidence for WNT5A as the causative gene in ADRS. Finally, we propose WNT5A mutation specificity in ADRS, which may affect interactions with other proteins in the Wnt pathway. SN - 1399-0004 UR - https://www.unboundmedicine.com/medline/citation/24716670/De_novo_WNT5A_associated_autosomal_dominant_Robinow_syndrome_suggests_specificity_of_genotype_and_phenotype_ L2 - https://doi.org/10.1111/cge.12401 DB - PRIME DP - Unbound Medicine ER -