Journal article
Search for genetic modifiers of IRF6 and genotype-phenotype correlations in Van der Woude and popliteal pterygium syndromes
American journal of medical genetics. Part A, Vol.161A(10), pp.2535-2544
10/2013
DOI: 10.1002/ajmg.a.36133
PMCID: PMC3898350
PMID: 23949966
Abstract
Van der Woude syndrome is the most common form of syndromic orofacial clefting, accounting for 1-2% of all patients with cleft lip and/or cleft palate. Van der Woude and popliteal pterygium syndromes are caused by mutations in IRF6, but phenotypic variability within and among families with either syndrome suggests that other genetic factors contribute to the phenotypes. The aim of this study was to identify common variants acting as genetic modifiers of IRF6 as well as genotype-phenotype correlations based on mutation type and location. We identified an association between mutations in the DNA-binding domain of IRF6 and limb defects (including pterygia). Although we did not detect formally significant associations with the genes tested, borderline associations suggest several genes that could modify the VWS phenotype, including FOXE1, TGFB3, and TFAP2A. Some of these genes are hypothesized to be part of the IRF6 gene regulatory network and may suggest additional genes for future study when larger sample sizes are also available. We also show that families with the Van de Woude phenotype but in whom no mutations have been identified have a lower frequency of cleft lip, suggesting there may be locus and/or mutation class differences in Van de Woude syndrome.
Details
- Title: Subtitle
- Search for genetic modifiers of IRF6 and genotype-phenotype correlations in Van der Woude and popliteal pterygium syndromes
- Creators
- Elizabeth J Leslie - Department of Pediatrics, University of Iowa, Iowa City, IAJennifer L Mancuso - Department of Medical Genetics, Mayo Clinic, Rochester, MNBrian C Schutte - Departments of Microbiology and Molecular Genetics, Pediatrics and Human Development, Michigan State University, East Lansing, MIMargaret E Cooper - Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PAKate M Durda - Department of Pediatrics, University of Iowa, Iowa City, IAJamie L'Heureux - Department of Pediatrics, University of Iowa, Iowa City, IATheresa M Zucchero - Department of Pediatrics, University of Iowa, Iowa City, IAMary L Marazita - Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PAJeffrey C Murray - Department of Pediatrics, University of Iowa, Iowa City, IA
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part A, Vol.161A(10), pp.2535-2544
- DOI
- 10.1002/ajmg.a.36133
- PMID
- 23949966
- PMCID
- PMC3898350
- NLM abbreviation
- Am J Med Genet A
- ISSN
- 1552-4825
- eISSN
- 1552-4833
- Publisher
- United States
- Grant note
- P30 ES005605 / NIEHS NIH HHS R01-DE013513 / NIDCR NIH HHS T32 GM008629 / NIGMS NIH HHS R01 DE016148 / NIDCR NIH HHS R37 DE008559 / NIDCR NIH HHS R37-DE008559 / NIDCR NIH HHS U01-DE020057 / NIDCR NIH HHS U01 DE020057 / NIDCR NIH HHS R01-DE016148 / NIDCR NIH HHS R01 DE013513 / NIDCR NIH HHS
- Language
- English
- Date published
- 10/2013
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984025364202771
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