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

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.