Van der Woude syndrome (VWS) is a rare autosomal dominant genetic disorder characterized by orofacial clefting and lip pits. Mutations in the transcription factor interferon regulatory factor 6 gene (IRF6) have been identified in individuals with VWS. We performed direct sequencing of the gene for molecular investigation of a proband with Bangladeshi-Malay ancestry. A novel transition mutation (c.113T>C), which resulted in an amino acid substitution (p.Ile38Thr) in the deoxyribonucleic acid-binding domain was detected. Testing of family members showed that the mutation segregated with the VWS phenotype for members of her immediate family. Although there is some phenotypic variability, all of the affected members are of the female gender.
AdzhubeiI.A., SchmidtS., PeshkinL., RamenskyV.E., GerasimovaA., BorkP., KondrashovA.S., SunyaevS.R.A method and server for predicting damaging missense mutations.Nat Methods.2010; 7: 248–249.
2.
de la GarzaG., SchleiffarthJ.R., DunnwaldM., MankadA., WeiratherJ.L., BondeG., ButcherS., MansourT.A., KousaY.A., FukazawaC.F.Interferon regulatory factor 6 promotes differentiation of the periderm by activating expression of Grainyhead-like 3.J Invest Dermatol.2013; 133: 68–77.
3.
DesmyterL., GhassibeM., RevencuN., BouteO., LeesM., FrancoisG., Verellen-DumoulinC., SznajerY., MonclaA., BenateauH.IRF6 screening of syndromic and a priori non-syndromic cleft lip and palate patients: identification of a new type of minor VWS sign.Mol Syndromol.2010; 1: 67–74.
4.
DoughertyM., KamelG., GrimaldiM., GfrererL., ShubinetsV., EthierR., HickeyG., CornellR.A., LiaoE.C.Distinct requirements for wnt9a and irf6 in extension and integration mechanisms during zebrafish palate morphogenesis.Development.2013; 140: 76–81.
KondoS., SchutteB.C., RichardsonR.J., BjorkB.C., KnightA.S., WatanabeY., HowardE., de LimaR.L., Daack-HirschS., SanderA.Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes.Nat Genet.2002; 32: 285–289.
7.
LittleH.J., RorickN.K., SuL.I., BaldockC., MalhotraS., JowittT., GakharL., SubramanianR., SchutteB.C., DixonM.J.Missense mutations that cause Van der Woude syndrome and popliteal pterygium syndrome affect the DNA-binding and transcriptional activation functions of IRF6.Hum Mol Genet.2009; 18: 535–545.
8.
Minones-SuarezL., Mas-VidalA., Fernandez-ToralJ., Llano-RivasI., Gonzalez-GarciaM.A novel mutation in the IRF6 gene associated with facial asymmetry in a family affected with Van der Woude syndrome.Pediatr Dermatol.2012; 29: 768–770.
O'NeillM.J.F.Van der Woude syndrome 2. 2014. Available at http://omim.org/entry/606713. Accessed November 9, 2015.
11.
OsoegawaK., VessereG.M., UtamiK.H., MansillaM.A., JohnsonM.K., RileyB.M., L'HeureuxJ., PfundtR., StaafJ., van der VlietW.A.Identification of novel candidate genes associated with cleft lip and palate using array comparative genomic hybridisation.J Med Genet.2008; 45: 81–86.
12.
SalahshourifarI., HalimA.S., SulaimanW.A., AriffinR., Naili Muhamad NorN., ZilfalilB.A.De novo interstitial deletion of 1q32.2–q32.3 including the entire IRF6 gene in a patient with oral cleft and other dysmorphic features.Cytogenet Genome Res.2011; 134: 83–87.
13.
StottmannR.W., BjorkB.C., DoyleJ.B., BeierD.R.Identification of a Van der Woude syndrome mutation in the cleft palate 1 mutant mouse.Genesis.2010; 48: 303–308.
14.
TanE.C., LimE.C., LeeS.T.De novo 2.3 Mb microdeletion of 1q32.2 involving the Van der Woude Syndrome locus.Mol Cytogenet.2013; 6: 31.
15.
ZuccheroT.M., CooperM.E., MaherB.S., Daack-HirschS., NepomucenoB., RibeiroL., CaprauD., ChristensenK., SuzukiY., MachidaJ.Interferon regulatory factor 6 (IRF6) gene variants and the risk of isolated cleft lip or palate.N Engl J Med.2004; 351: 769–780.
