Presentation Blocks: 03-22-2018 - Thursday - 03:45 PM - 05:00 PM

Title: Novel IRF6 Mutation: Puerto Rican van der Woude Syndrome Family


Ada Toraño (Presenter)
University of Puerto Rico

TAMARA BUSCH, University of Iowa
Carolina Bello, University of Puerto Rico
Natalio Debs, School of Dental Medicine University of Puerto Rico
Augusto Elias-Boneta, University of Puerto Rico
Maria Salcedo, School of Dental Medicine University of Puerto Rico
Lydia López-Del Valle, School of Dental Medicine University of Puerto Rico
Mairim Soto-Ortiz, School of Dental Medicine University of Puerto Rico
José Cordero, University of Georgia
Mary Marazita, University of Pittsburgh
JEFFREY MURRAY, University of Iowa
Azeez Butali, University of Iowa
Carmen Buxó-Martínez, School of Dental Medicine University of Puerto Rico


Objectives: Cleft lip and palate (CL/P) is the second most common congenital birth defect and can be classified as either syndromic or nonsyndromic. About 30% of orofacial clefts are syndromic. The most common syndrome associated with orofacial clefts is van der Woude Syndrome (VWS, OMIM119300). About 75% of cases with this syndrome have mutations in the IRF6 gene.

Methods: In this study, 22 Puerto Rican proband (child) samples with CL/P were analyzed using Sanger sequencing. A novel IRF6 mutation was found in one proband with a cleft of the hard palate. This was verified by reverse sequencing of the proband and by sequencing DNA from the parents.

Results: A novel damaging IRF6 mutation was confirmed in both the mother and the proband who also both presented lip pits, demonstrating a hereditary pattern of VWS and the presence of VWS was confirmed in the family. The IRF6 mutation resulted in an amino acid change from phenylalanine to tyrosine in the position 36 (F36Y). It is located in the protein binding domain and expands the genotype/phenotype correlations for IRF6 and VWS (Leslie et al, 2013). According to Polyphen/SIFT, this mutation is predicted to be deleterious or probably damaging. One other amino acid change at position 36 in VWS has also been reported (F36Y).

Conclusions: A novel, potentially damaging mutation in the IRF6 gene was found in a proband with cleft palate and lip pits, and in the proband’s mother with lip pits only. Identifying mutations in this gene is important because, if the parent of the proband is affected or has an IRF6 pathogenic variant, the risk to the siblings of inheriting the pathogenic variant is increased by 50%. This information is essential for accurate genetic counselling for families.