Search for genetic modifiers of IRF6 and genotype–phenotype correlations in Van der Woude and popliteal pterygium syndromes. Issue 10 (15th August 2013)

• Record Type: Journal Article
• Authors: Leslie, Elizabeth J.; Mancuso, Jennifer L.; Schutte, Brian C.; Cooper, Margaret E.; Durda, Kate M.; L'Heureux, Jamie; Zucchero, Theresa M.; Marazita, Mary L.; Murray, Jeffrey C.
• Is Part Of: American journal of medical genetics. Volume 161:Issue 10(2013:Oct.)
• Page Start: 2535
• Page End: 2544
• Publication Date: 2013-08-15
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36133
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>ABSTRACT</title> <sec id="ajmga36133-sec-0001" sec-type="section"> <p>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 <italic>IRF6</italic>, 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 <italic>IRF6</italic> as well as genotype–phenotype correlations based on mutation type and location. We identified an association between mutations in the DNA‐binding domain of <italic>IRF6</italic> 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 <italic>FOXE1</italic>, <italic>TGFB3</italic>, and <italic>TFAP2A</italic>. 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. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>