Interferon regulatory factor 6 (IRF6) and fibroblast growth factor receptor 1 (FGFR1) contribute to human tooth agenesis

Abstract

Phenotypic characteristics expressed in syndromes give clues to the factors involved in the cause of isolated forms of the same defects. We investigated two genes responsible for craniofacial syndromes, FGFR1 and IRF6, in a collection of families with isolated tooth agenesis. Cheek swab samples were obtained for DNA analysis from 116 case/parent trios. Probands had at least one developmentally missing tooth, excluding third molars. In addition, we studied 89 cases and 50 controls from Ohio to replicate any positive findings. Genotyping was performed by kinetic polymerase chain-reaction or TaqMan assays. Linkage disequilibrium analysis and transmission distortion of the marker alleles were performed. The same variants in the IRF6 gene that are associated with isolated orofacial clefts are also associated with human tooth agenesis (rs861019, P = 0.058; rs17015215-V274I, P = 0.0006; rs7802, P = 0.004). Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. The craniofacial phenotypic characteristics of these syndromes include oral clefts and preferential tooth agenesis of incisors and premolars, besides pits on the lower lips. Also it appears that preferential premolar agenesis is associated with FGFR1 (P = 0.014) and IRF6 (P = 0.002) markers. There were statistically significant data suggesting that IRF6 interacts not only with MSX1 (P = 0.001), but also with TGFA (P = 0.03).

A genome wide linkage scan for cleft lip and palate and dental anomalies

“…Expression analysis of these tissues during development also supports an overlapping role [Vieira et al, 2007b]. Our study provides further evidence that common genetic factors may contribute to both CL/P and dental anomalies.…”

“…This region is relatively close to IRF6 (1q32.2). Our previous work found a strong association between IRF6 and clefts [Zucchero et al, 2004;Vieira et al, 2007a], and isolated tooth agenesis [Vieira et al, 2007b]. However, we were not able to identify the functional genetic variant yet.…”

Single nucleotide polymorphisms in new candidate genes are associated with bone mineral density and fracture risk

“…FGFR1 (member of receptor tyrosine kinases) is expressed on both osteoclasts and osteoblasts, and influences osteogenic differentiation of stem cells (23)(24)(25). Its mutations and haplotypes are associated with skeletal deformities seen in Pfeiffer and Kallmann syndromes, human tooth agenesis (26), and normal variations in craniofacial shape (27). In a recent study, decreased expression of FGFR1 in osteoporotic bone tissue was demonstrated (13).…”

Candidate Genes for Cleft Lip and Palate: Review

“…Ayrıca, diş eksikliğine neden olan en önemli aday genlerden biri olarak belirtilmektedir. 3,13,35,57 "T-BOX TRANSCRIPTION FACTOR (TBX22)"…”