The most distinguishing feature of MSX1-associated oligodontia is the frequent (75%) absence of maxillary first bicuspids, while the most distinguishing feature of PAX9-associated oligodontia is the frequent (> 80%) absence of the maxillary and mandibular second molars.
Our finding suggests that this transition might be the first described mutation of MSX1 that might be responsible for oligodontia and showing incomplete penetrance.
Considering the discrepancy between the high incidence rate of agenesis and the relatively small number of reported causative mutations in PAX9, MSX1 and AXIN2 genes, the genetic contribution to oligodontia probably is much more heterogeneous than expected so far.
Coupling these new clinical findings with results from recent molecular studies, we suggest that transcription factors such as MSX1 and PAX9, which have been associated with agenesis of molars, might be involved in the genetic control of Mn.I2.C transposition and PDC, tooth malpositions connected here with the specific expression of posterior-field (M3) hypodontia.
The strategy in this study was to use the variation in the number of teeth in the affected individuals of three mutant families with hypodontia, to determine the relative influence (relative molecular morphogenetic field) of MSX 1 and PAX 9 genes on the dental field.
The absence of a mutation in exons 1 and 2 of MSX1 suggested that allelic mutations in the coding region of MSX1 are not associated with this phenotypically distinct form of oligodontia.
Our results indicate that inactivation of MSX1 gene in humans must have a highly selective effect on dentition, and other genes must be involved in the cause of hypodontia in humans.
The pairwise lod-scores regarding the intragenic microsatellites in the MSX1 and MSX2 genes at a recombination fraction of 0.0 were -3.1 and -3.0, respectively, thus excluding these genes as causative loci for hypodontia in these families.
The Msx1-/Msx1- phenotype is similar to human cleft palate, and provides a genetic model for cleft palate and oligodontia in which the defective gene is known.
All available patients with non-syndromic oligodontia (n = 20) treated at the Department of Orthodontics, University of Giessen, Germany between 1986 and 2013 as well as their family members were analyzed for mutations in the WNT10A gene.
Study of rs12532, rs8670 Polymorphism of Msh Homeobox 1 (MSX1), rs61754301, rs4904155 Polymorphism of Paired Box Gene 9 (PAX9), and rs2240308 Polymorphism of Axis Inhibitor Protein 2 (AXIN2) Genes in Nonsyndromic Hypodontia.