Genetic analysis of familial non-syndromic primary failure of eruption

To cite this article:Frazier-Bowers SA, Simmons D, Koehler K, Zhou J:Genetic analysis of familial non-syndromic primary failure of eruptionOrthod Craniofac Res 2009;12:74-81 Frazier-Bowers SA, Simmons D, Koehler K, Zhou J While some eruption disorders occur as part of a medical syndrome, primary failure of eruption (PFE) - defined as a localized failure of secondary tooth eruption - exists without systemic involvement. Recent studies support that heredity may play an important role in the pathogenesis of PFE. The objective of our human genetic study is to investigate the genetic contribution to PFE. Four candidate genes POSTN, RUNX2, AMELX, and AMBN) were investigated because of their relationship to tooth eruption or putative relationship to each other. Families and individuals were ascertained based on the clinical diagnosis of PFE. Pedigrees were constructed and analyzed by inspection to determine the mode of inheritance in four families. The candidate genes were directly sequenced for both unrelated affected individuals and unaffected individuals. A genome wide scan using 500 microsatellite markers followed by linkage analysis was carried out for one family. Pedigree analysis of families suggests an autosomal dominant inheritance pattern with complete penetrance and variable expressivity. Sequence analysis revealed two non-functional polymorphisms in the POSTN gene and no other sequence variations in the remaining candidate genes. Genotyping and linkage analysis of one family yielded a LOD score of 1.51 for markers D13S272; D15S118 and D17S831 on chromosomes 13, 15 and 17 respectively. While LOD scores were not significant evidence of linkage, extension of current pedigrees and novel SNP chip technology holds great promise for identification of a causative locus for PFE.