Abstract
Cleft lip with or without cleft palate is the most frequent craniofacial malformation in humans (∼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.
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Acknowledgements
We thank Jeffrey C Murray and Theresa Zucchero for providing us with SNP materials and for help with study design. We are grateful for all the families for their participation in the study. The studies were supported by the Fonds Spéciaux de Recherche – University of Louvain Medical School, the Fonds national de la recherche scientifique (FNRS) (to MV, a ‘maître de recherche du FNRS’). M Ghassibé was supported by a fellowship from FRIA (Fonds pour la formation à la recherche dans l’industrie et dans l’agriculture).
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Ghassibé, M., Bayet, B., Revencu, N. et al. Interferon regulatory factor-6: a gene predisposing to isolated cleft lip with or without cleft palate in the Belgian population. Eur J Hum Genet 13, 1239–1242 (2005). https://doi.org/10.1038/sj.ejhg.5201486
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DOI: https://doi.org/10.1038/sj.ejhg.5201486
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