title: Interferon regulatory factor-6: a gene predisposing to isolated cleft lip with or without cleft palate in the Belgian population.
abstract: Cleft lip with or without cleft palate is the most frequent craniofacial malformation in humans ( approximately 1/700). Its etiology is multifactorial; some are a result of a genetic mutation, while others may be due to environmental factors, with genetic predisposition playing an important role. The prevalence varies widely between populations and the mode of inheritance remains controversial. 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. Moreover IRF6 has been associated with nonsyndromic cleft of the palate (CL/P) in two separate studies. We investigated the role of IRF6 in a set of 195 trios from Belgium. Cleft occurred as an isolated feature. We studied association of the IRF6 locus using two variants: one in the IRF6 gene and the other 100 kpb 3' of the gene. Our independent study group confirms that the IRF6 locus is associated with nonsyndromic cleft lip with or without palate. This result, with previous studies performed in the United States and Italy, shows for the first time the implication of IRF6 in isolated CL/P in northern Europe. It is likely that association to this locus can be identified in various populations and that the IRF6 locus thus represents an important genetic modifier for this multifactorial malformation.
authors.affiliation: Laboratory of Human Molecular Genetics, Christian de Duve Institute of Cellular Pathology and University of Louvain Medical School, Brussels, Belgium.
authors.forename: Michella
authors.initials: M
authors.lastname: Ghassibé
authors.forename: Benedicte
authors.initials: B
authors.lastname: Bayet
authors.forename: Nicole
authors.initials: N
authors.lastname: Revencu
authors.forename: Christine
authors.initials: C
authors.lastname: Verellen-Dumoulin
authors.forename: Yves
authors.initials: Y
authors.lastname: Gillerot
authors.forename: Romain
authors.initials: R
authors.lastname: Vanwijck
authors.forename: Miikka
authors.initials: M
authors.lastname: Vikkula
mesh_terms: D001530:Belgium; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors