A novel mutation in the <i>IRF6</i> gene associated with facial asymmetry in a family affected with Van der Woude Syndrome

Miñones-Suarez, Lorena; Mas-Vidal, Alberto; Fernández-Toral, Joaquín; Llano-Rivas, Isabel; González-García, Manuel

doi:10.1111/j.1525-1470.2011.01575.x

Cited by 9 publications

(18 citation statements)

References 5 publications

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“…Since discovery of IRF6 , case reports and case series from a wide geographical distribution have expanded the phenotypic spectrum of VWS (Kayano et al, ; Kim et al, ; Shotelersuk et al, ; Wang et al, ; Gatta et al, ; Ghassibe et al, ; Matsuzawa et al, ; Item et al, ; Ye et al, ; Du et al, ; Brosch et al, ; Paranaiba et al, ; Tan et al, ; de Lima et al, ; Yeetong et al, ; Malik et al, ; Scioletti et al, ; Birkeland et al, ; Minones‐Suarez et al, ; Salahshourifar et al, ). While most studies of VWS have identified point mutations in IRF6 , deletions as large as 2.98 Mb, involving 25 genes, have also been reported (Sander et al, ; Schutte et al, ; Salahshourifar et al, ).…”

Section: Mutations In Irf6 Cause Vws and Ppsmentioning

confidence: 99%

“…Both the cartoon and sphere models were created using PyMol. Scioletti et al, 2010;Birkeland et al, 2011;Minones-Suarez et al, 2011;Salahshourifar et al, 2011). While most studies of VWS have identified point mutations in IRF6, deletions as large as 2.98 Mb, involving 25 genes, have also been reported (Sander et al, 1994;Schutte et al, 1999;Salahshourifar et al, 2011).…”

Section: Mutations In Irf6 Cause Vws and Ppsmentioning

confidence: 99%

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Toward an orofacial gene regulatory network

Kousa

Schutte

2015

Developmental Dynamics

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Orofacial clefting is a common birth defect with significant morbidity. A panoply of candidate genes have been discovered through synergy of animal models and human genetics. Among these, variants in Interferon Regulatory Factor 6 (IRF6) cause syndromic orofacial clefting and contribute risk toward isolated cleft lip and palate (1/700 live births). Rare variants in IRF6 can lead to Van der Woude Syndrome (1/35,000 live births) and Popliteal Pterygium Syndrome (1/300,000 live births). Furthermore, IRF6 regulates GRHL3 and rare variants in this downstream target can also lead to Van der Woude Syndrome. In addition, a common variant (rs642961) in the IRF6 locus is found in 30% of the world’s population and contributes risk for isolated orofacial clefting. Biochemical studies revealed that rs642961 abrogates one of four AP-2alpha binding sites. Like IRF6 and GRHL3, rare variants in TFAP2A can also lead to syndromic orofacial clefting with lip pits (Branchio-oculo-facial Syndrome). The literature suggests that AP-2alpha, IRF6 and GRHL3 are part of a pathway that is essential for lip and palate development. In addition to updating the pathways, players and pursuits, this review will highlight some of the current questions in the study of orofacial clefting.

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Section: Mutations In Irf6 Cause Vws and Ppsmentioning

confidence: 99%

Section: Mutations In Irf6 Cause Vws and Ppsmentioning

confidence: 99%

Toward an orofacial gene regulatory network

Kousa

Schutte

2015

Developmental Dynamics

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“…For example, Bartsocas-Papas syndrome is a recessive pterygia syndrome characterized by multiple popliteal pterygia, CL/P, ankyloblepharon, synechia, and syndactyly. This disorder is caused by mutations in Receptor-interacting serine/threonine kinase 4 (RIPK4) (Kalay et al 2012;Mitchell et al 2012). As noted earlier, the cardinal features of EEC are similar to some of the features of VWS.…”

Section: Evidence For Genetic Modifiers In Vws and Ppsmentioning

confidence: 71%

“…Identification of genes causing these syndromes has been very successful ) and has been further facilitated by advances in sequencing technology. Exome sequencing recently identified genes causing Kabuki syndrome (Ng et al 2010a) and Bartsocas-Papas syndrome (Kalay et al 2012;Mitchell et al 2012).…”

Section: Mendelian Forms Of Orofacial Cleftsmentioning

confidence: 99%

“…Genes causing other syndromes with lip pits include MLL2 (Kabuki syndrome, Ng et al (2010a)) and TFAP2A (branchio-oculofacial syndrome, Milunsky et al (2008)). With the exception of MLL2, the other genes mentioned here have known connections to IRF6 through its upstream enhancer element, MCS-9.7 Moretti et al 2010;Thomason et al 2010;Mitchell et al 2012) and p63 (McDade et al 2012;Mitchell et al 2012 In 1942, Fogh-Anderson first proposed that genetic factors contribute to NSCL/P after observing an increased frequency of clefting in relatives of a patient with a cleft (Fogh- Andersen 1942). A genetic component to clefting was later confirmed by segregation analysis (Marazita et al 1984) and twin studies (Mitchell 2002).…”

Section: Evidence For Genetic Modifiers In Vws and Ppsmentioning

confidence: 99%

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Advances in understanding the genetic architecture of cleft lip and palate disorders

Leslie¹

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Novel IRF6 mutations in families with Van Der Woude syndrome and popliteal pterygium syndrome from sub‐Saharan Africa

Butali

Mossey

Adeyemo

et al. 2014

Molec Gen & Gen Med

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Orofacial clefts (OFC) are complex genetic traits that are often classified as syndromic or nonsyndromic clefts. Currently, there are over 500 types of syndromic clefts in the Online Mendelian Inheritance in Man (OMIM) database, of which Van der Woude syndrome (VWS) is one of the most common (accounting for 2% of all OFC). Popliteal pterygium syndrome (PPS) is considered to be a more severe form of VWS. Mutations in the IRF6 gene have been reported worldwide to cause VWS and PPS. Here, we report studies of families with VWS and PPS in sub-Saharan Africa. We screened the DNA of eight families with VWS and one family with PPS from Nigeria and Ethiopia by Sanger sequencing of the most commonly affected exons in IRF6 (exons 3, 4, 7, and 9). For the VWS families, we found a novel nonsense variant in exon 4 (p.Lys66X), a novel splice-site variant in exon 4 (p.Pro126Pro), a novel missense variant in exon 4 (p.Phe230Leu), a previously reported splice-site variant in exon 7 that changes the acceptor splice site, and a known missense variant in exon 7 (p.Leu251Pro). A previously known missense variant was found in exon 4 (p.Arg84His) in the PPS family. All the mutations segregate in the families. Our data confirm the presence of IRF6-related VWS and PPS in sub-Saharan Africa and highlights the importance of screening for novel mutations in known genes when studying diverse global populations. This is important for counseling and prenatal diagnosis for high-risk families.

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A novel mutation in the IRF6 gene associated with facial asymmetry in a family affected with Van der Woude Syndrome

Abstract: This report describes a novel missense mutation in the interferon regulation factor 6 (IRF6) gene associated to facial asymmetry. This new feature widens the phenotype spectrum of Van der Woude syndrome (VWS).

Cited by 9 publications

References 5 publications

Toward an orofacial gene regulatory network

Toward an orofacial gene regulatory network

Advances in understanding the genetic architecture of cleft lip and palate disorders

Novel IRF6 mutations in families with Van Der Woude syndrome and popliteal pterygium syndrome from sub‐Saharan Africa

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