Novel IRF6 mutations in Chinese Han families with Van der Woude syndrome

Abstract Background Interferon Regulatory Factor 6 (IRF6) gene encodes a member of the IRF family of transcription factors. Mutations in IRF6 cause Van der Woude Syndrome (VWS), which is the most common malformation of syndromic orofacial clefts in humans. Methods Here, we performed sequencing studies of six families with VWS in the Chinese Han population. The entire IRF6‐coding region and the exon–intron boundaries including exons 3–8 and part of exon 9 were screened among all the collected family members by Sanger sequencing. Results We found a novel splice site variant c.175‐6T>A, two novel missense variants (p.Lys66Arg and p.Pro107Thr), in addition with a previously reported missense variant (p.Leu87Phe), which were all located in and nearby exon 4 of IRF6. Meanwhile, a novel frameshift variant p.G257Vfs*46 in exon 7 of IRF6 was also detected. All the mutations presented to be co‐segregated in each family. Conclusion Our study has advanced the understanding of the genetic architecture of VWS and provides the basis for genetic counseling, antenatal diagnosis, and gene therapy of high risk groups.