To test whether DNA variants in regulatory elements cause VWS, we sequenced three conserved elements near IRF6 in 70 VWS families that lack an etiologic mutation within IRF6 exons.
In humans, mutations in the transcription factor interferon regulatory factor 6 (IRF6) underlie Van der Woude syndrome and popliteal pterygium syndrome.
Members from two Van der Woude syndrome (VWS) families were screened to determine the prevalence of interferon regulatory factor 6 (IRF6) as a disease‑causing gene and to analyze the interrelationships between patient genotype and phenotype.
Since the E349V change may disturb the hydrophobic core and affect regulatory activity of IRF6, it is most likely that the mutation is causative for VWS in this family.
IRF6 mutations were identified in four out of five VWS families examined, which strongly suggests that mutations in IRF6 are responsible for VWS in this population.
A family history of cleft lip and palate was noted, and interferon regulatory factor 6 ( IRF6) sequencing revealed a heterozygous variant, confirming the diagnosis of van der Woude syndrome.
Mutations in interferon regulatory factor 6 (IRF6) account for ∼70% of cases of Van der Woude syndrome (VWS), the most common syndromic form of cleft lip and palate.
In the current investigation, we have determined the sequence to which IRF6 binds and used this sequence to analyse the effect of VWS- and PPS-associated mutations in the DNA-binding domain of IRF6.
The interferon regulatory factor-6 (IRF6) gene has been shown to harbor mutations in patients with van der Woude syndrome, a dominant form of clefts associated with small pits of the lower lip.
The interferon regulatory factor 6 (IRF6), the gene that causes van der Woude syndrome has been shown to be associated with nonsyndromic cleft lip with or without palate in several populations.
Since IRF6 mutations in a significant portion of VWS patients remain undetected by conventional sequencing analysis, it may be important to search for a large deletion in those patients.