{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T21:00:54Z","timestamp":1790974854258,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2013,8,15]],"date-time":"2013-08-15T00:00:00Z","timestamp":1376524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>Van der Woude syndrome is the most common form of syndromic orofacial clefting, accounting for 1\u20132% of all patients with cleft lip and\/or cleft palate. Van der Woude and popliteal pterygium syndromes are caused by mutations in <jats:italic>IRF6<\/jats: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 <jats:italic>IRF6<\/jats:italic> as well as genotype\u2013phenotype correlations based on mutation type and location. We identified an association between mutations in the DNA\u2010binding domain of <jats:italic>IRF6<\/jats: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 <jats:italic>FOXE1<\/jats:italic>, <jats:italic>TGFB3<\/jats:italic>, and <jats:italic>TFAP2A<\/jats: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. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36133","type":"journal-article","created":{"date-parts":[[2013,8,15]],"date-time":"2013-08-15T20:28:00Z","timestamp":1376598480000},"page":"2535-2544","source":"Crossref","is-referenced-by-count":25,"title":["Search for genetic modifiers of IRF6 and genotype\u2013phenotype correlations in Van der Woude and popliteal pterygium syndromes"],"prefix":"10.1002","volume":"161","author":[{"given":"Elizabeth J.","family":"Leslie","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C.","family":"Schutte","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Molecular Genetics Pediatrics and Human Development Michigan State University East Lansing Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret E.","family":"Cooper","sequence":"additional","affiliation":[{"name":"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 Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate M.","family":"Durda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"L'Heureux","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa M.","family":"Zucchero","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary L.","family":"Marazita","sequence":"additional","affiliation":[{"name":"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 Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey C.","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,8,15]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3031"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.580"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.333"},{"key":"e_1_2_6_5_1","first-page":"99","article-title":"Genetic epidemiology and control of genetic expression in van der Woude syndrome","volume":"2","author":"Burdick AB","year":"1986","journal-title":"J Craniofac Genet Dev Biol Suppl"},{"key":"e_1_2_6_6_1","first-page":"181","article-title":"Genetic analysis in families with van der Woude syndrome","volume":"5","author":"Burdick AB","year":"1985","journal-title":"J Craniofac Genet Dev Biol"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e318197a49a"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2933"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22786"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.08.005"},{"key":"e_1_2_6_11_1","first-page":"503","article-title":"Popliteal pterygium syndrome. 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