The European Journal of Orthodontics Advance Access originally published online on January 21, 2008
The European Journal of Orthodontics 2008 30(2):169-175; doi:10.1093/ejo/cjm097
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Familial non-syndromic cleft lip and palate—analysis of the IRF6 gene and clinical phenotypes
* Department of Orthodontics, Karolinska Institutet, Huddinge
** Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge
*** Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Sweden
**** Department of Reconstructive Plastic Surgery, Karolinska University Hospital Solna, Sweden
***** Department of Stockholm Craniofacial Team, Karolinska University Hospital Solna, Sweden
Address for correspondence Marie Pegelow, Department of Orthodontics, Section for Jaw Orthopaedics, Box 4064, Karolinska Institutet, 141 04 Huddinge, Sweden, E-mail: marie.pegelow{at}ki.se
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Abstract |
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The aim of this study was to characterize Swedish families with non-syndromic cleft lip and/or palate (NSCL/P) for mutations or other sequence variants in the interferon regulatory factor 6 (IRF6) gene, as well as to describe their cleft phenotypes and hypodontia. Seventeen Swedish families with at least two family members with NSCL/P were identified and clinically evaluated. Extracted DNA from blood samples was used for IRF6 mutation screening. Exonic fragments of the IRF6 gene were sequenced and chromatograms were inspected. Statistical analysis was undertaken with marker- and haplotype association tests.
No disease-associated IRF6 mutation could be determined in the families analyzed. One new and seven known single nucleotide polymorphisms (SNPs) were detected. The A allele of SNP rs861019 in exon 2 and the G allele of SNP rs7552506 in intron 3 showed association with cleft lip and palate (CLP; odds ratios of 3.1 and 5.45, respectively). Hypodontia was observed more commonly in individuals affected with CL/P as compared with family members without a cleft (P < 0.01). The hypodontia most often affected the cleft area, possibly representing a secondary effect. The distribution of cleft phenotypes in 15 of the 17 families with NSCL/P differed from the mixed cleft types seen in Van der Woude syndrome (VWS), in that CLP did not occur together with an isolated cleft palate within the same family. It was concluded that mutations of the IRF6 gene are not a common cause for cleft predisposition in Swedish NSCL/P families.