Interferon Regulatory Factor 6 (IRF6) Gene Variants and the Risk of Isolated Cleft Lip or Palate

Abstract

DNA-sequence variants associated with IRF6 are major contributors to cleft lip, with or without cleft palate. The contribution of variants in single genes to cleft lip or palate is an important consideration in genetic counseling.

Infants with Bochdalek diaphragmatic hernia: Sibling precurrence and monozygotic twin discordance in a hospital‐based malformation surveillance program

“…The discovery of mutations in the interferon regulatory factor 6 gene (IRF6) as the cause of lip pit or van der Woude syndrome could be a model for identifying multifactorial genetic changes contributing to CDH. Specifically, mutations in both the IRF6 protein binding domain and the DNA binding domain produce van der Woude syndrome; recent studies demonstrate that a common variant in IRF6 increases the risk for isolated cleft lip and palate [Kondo et al, 2002;Kayano et al, 2003;Zucchero et al, 2004;Scapoli et al, 2005]. Thus, possible mutations or clusters of polymorphisms in FOG2, WT1 and, other as yet unidentified major development genes or their downstream targets, could contribute to multifactorial causation of CDH.…”

Presence of sequence and SNP variation in the IRF6 gene in healthy residents of Guangdong Province

“…There was no kinship among them. (2) No family history of CL/P. (3) No other congenital disease or malformation, or major organ disease.…”

A Novel Heterozygous Mutation (F252Y) in Exon 7 of the IRF6 Gene is Associated with Oral Squamous Cell Carcinomas

“…While the N-terminal DNA-binding domain is essential for IRF proteins to bind with the respective promoter region of genes it regulates, the C-terminal IAD is required for protein-protein interactions (Tamura et al, 2008;Savitsky et al, 2010). Of the nine IRFs (IRF1 to IRF9) that have been reported so far, IRF6 is known to play a vital role in the development of craniofacial region, by regulating cellular differentiation and proliferation (Zucchero et al, 2004). Mutational alterations in the coding regions of IRF6 gene were first identified in subjects with van der Woude syndrome (VWS), which is known to be the most common of all the Mendelian malformation syndromes (Zucchero et al, 2004).…”

“…Of the nine IRFs (IRF1 to IRF9) that have been reported so far, IRF6 is known to play a vital role in the development of craniofacial region, by regulating cellular differentiation and proliferation (Zucchero et al, 2004). Mutational alterations in the coding regions of IRF6 gene were first identified in subjects with van der Woude syndrome (VWS), which is known to be the most common of all the Mendelian malformation syndromes (Zucchero et al, 2004). Subjects with VWS have either cleft lip, cleft palate or cleft lip with cleft palate (CL/CP/ CLP) and importantly, a labial pit that distinguishes VWS from non-syndromic CL/CP/CLP (Zucchero et al, 2004).…”

“…Mutational alterations in the coding regions of IRF6 gene were first identified in subjects with van der Woude syndrome (VWS), which is known to be the most common of all the Mendelian malformation syndromes (Zucchero et al, 2004). Subjects with VWS have either cleft lip, cleft palate or cleft lip with cleft palate (CL/CP/ CLP) and importantly, a labial pit that distinguishes VWS from non-syndromic CL/CP/CLP (Zucchero et al, 2004). The exon 7 of IRF6 gene encodes for major region of the C-terminal IAD region and hence mutations within this region may be expected cause functional impairment.…”