Genomic Strategy Identifies a Missense Mutation in WD-Repeat Domain 65 (WDR65) in an Individual with Van der Woude Syndrome

Nicholas K Rorick; Akira Kinoshita; Jason Weirather; Myriam Peyrard-Janvid; Renata L. L Ferreira de Lima; Martine Dunnwald; Alan L Shanske; Danilo Moretti-Ferreira; Hannele Koillinen; Juha Kere; Maria A Mansilla; Jeffrey C Murray; Steve L Goudy; Brian C Schutte

doi:10.1002/ajmg.a.33980

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Genomic Strategy Identifies a Missense Mutation in WD-Repeat Domain 65 (WDR65) in an Individual with Van der Woude Syndrome

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Genomic Strategy Identifies a Missense Mutation in WD-Repeat Domain 65 (WDR65) in an Individual with Van der Woude Syndrome

Nicholas K Rorick, Akira Kinoshita, Jason Weirather, Myriam Peyrard-Janvid, Renata L. L Ferreira de Lima, Martine Dunnwald, Alan L Shanske, Danilo Moretti-Ferreira, Hannele Koillinen, Juha Kere, …

American journal of medical genetics. Part A, Vol.155(6), pp.1314-1321

06/2011

DOI: 10.1002/ajmg.a.33980

PMCID: PMC3753799

PMID: 21574244

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https://www.ncbi.nlm.nih.gov/pmc/articles/3753799View

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Abstract

Genetic variation in the transcription factor Interferon Regulatory Factor 6 ( IRF6 ) causes and contributes risk for oral clefting disorders. We hypothesized that genes regulated by IRF6 are also involved in oral clefting disorders. We used five criteria to identify potential IRF6 target genes; differential gene expression in skin taken from wild type and Irf6 -deficient murine embryos, localization to the Van der Woude syndrome 2 ( VWS2 ) locus at 1p36–1p32, overlapping expression with Irf6 , presence of a conserved predicted binding site in the promoter region, and a mutant murine phenotype that was similar to the Irf6 mutant mouse. Previously, we observed altered expression for 573 genes; 13 were located in the murine region syntenic to the VWS2 locus. Two of these genes, Wdr65 and Stratifin , met four of five criteria. Wdr65 was a novel gene that encoded a predicted protein of 1250 amino acids with two WD domains. As potential targets for Irf6 regulation, we hypothesized that disease-causing mutations will be found in WDR65 and Stratifin in individuals with VWS or VWS-like syndromes. We identified a potentially etiologic missense mutation in WDR65 in a person with VWS who does not have an exonic mutation in IRF6 . The expression and mutation data were consistent with the hypothesis that WDR65 was a novel gene involved in oral clefting.

Mutation

Gene Expression

transcription factor

cleft lip and palate

syndrome

genomic

microvilli

WD domain

Details

Title: Subtitle: Genomic Strategy Identifies a Missense Mutation in WD-Repeat Domain 65 (WDR65) in an Individual with Van der Woude Syndrome
Creators: Nicholas K Rorick - Department of Pediatrics, University of Iowa, Iowa City, IA, USA
Akira Kinoshita - Department of Pediatrics, University of Iowa, Iowa City, IA, USA
Jason Weirather - Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA, USA
Myriam Peyrard-Janvid - Department of BioNut, Novum, Karolinska Institutet, Huddinge, Sweden
Renata L. L Ferreira de Lima - General Biology, Federal University of Bahia, Salvador, Bahia, Brazil
Martine Dunnwald - Department of Pediatrics, University of Iowa, Iowa City, IA, USA
Alan L Shanske - Center for Craniofacial Disorders, Children's Hospital at Montefiore, Bronx, NY, USA
Danilo Moretti-Ferreira - Servico de Aconselhamento Genetico, Universidade Estadual Paulista, Botucatu, SP, Brazil
Hannele Koillinen - Department of Pediatrics, Turku University Hospital, Turku, Finland
Juha Kere - Department of BioNut, Novum, Karolinska Institutet, Huddinge, Sweden
Maria A Mansilla - Department of Pediatrics, University of Iowa, Iowa City, IA, USA
Jeffrey C Murray - Department of Pediatrics, University of Iowa, Iowa City, IA, USA
Steve L Goudy - Department of Otolaryngology, Vanderbilt University, Nashville, TN, USA
Brian C Schutte - Departments of Microbiology and Molecular Genetics and Pediatrics and Human Development, Michigan State University, East Lansing, MI, USA
Resource Type: Journal article
Publication Details: American journal of medical genetics. Part A, Vol.155(6), pp.1314-1321
DOI: 10.1002/ajmg.a.33980
PMID: 21574244
PMCID: PMC3753799
NLM abbreviation: Am J Med Genet A
ISSN: 1552-4825
eISSN: 1552-4833
Grant note: R37 DE008559 || DE / National Institute of Dental and Craniofacial Research : NIDCR
Language: English
Date published: 06/2011
Academic Unit: Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research; Iowa Institute of Human Genetics
Record Identifier: 9984025375202771

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