The occurrence of non-syndromic still remains poorly understood, but in recent years some cases have been reported where mutations or polymorphisms of PAX9 and MSX1 had been associated with non-syndromic oligodontia.
DNA sequencing of the MSX1 gene revealed two mutations in the two patients with oligodontia: a heterozygotic silent mutation, c.348C>T (P.Gly116=), in exon 1 and a homozygotic deletion of 11 nucleotides (c.469+56delins GCCGGGTGGGG) in the intron.
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.
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.
We identified two novel MSX1 variants with an amino acid substitution within the homeodomain; Thr174Ile (T174I) from a sporadic hypodontia case and Leu205Arg (L205R) from a familial oligodontia case.
Previous studies have indicated that mutations in the homeobox gene MSX1, paired domain transcription factor PAX9, and EDA are associated with non-syndromic oligodontia.
In conclusion, the results of the present study showed that the variant genotype and variant T allele of the MSX1rs8670 SNP increased the risk of hypodontia in the studied population.
In conclusion, these meta-analysis results demonstrated that polymorphisms in the rs1095 region of the MSX1 gene may influence the transcriptional activity of this gene and are associated with hypodontia in humans.
Our results for the first time demonstrates that mutations in MSX1 gene might play an important role in hypodontia cases involving pre-molars and is a risk factor for this ethnic population mainly of Arabs and is first report linking these mutations with tooth agenesis.
The objective of the present study was to search for Msh homeobox 1 (MSX1), paired box gene 9 (PAX9), ectodysplasin‑A (EDA) and axis inhibition protein 2 (AXIN2) variants in a family with isolated oligodontia and analyse the pathogenesis of mutations that result in oligodontia phenotypes.
Oligodontia as well as hypodontia (lack of one or more permanent teeth) are highly heritable conditions associated with mutations in the AXIN2, MSX1, PAX9, EDA, and EDAR genes.
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.
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.