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 this study, a novel frameshift mutation, the twenty-nucleotide deletion (c.128_147del20, p.Met43Serfsx125), in exon1 of MSX1 was detected in a Chinese family causing autosomal dominant nonsyndromic oligodontia.
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.
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.
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.
Recently, several genes have been reported with mutations or variants that underlie a number of syndromic and non-syndromic forms of oligodontia including MSX1, PAX9, AXIN2, EDA and WNT10A.
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.
Our results demonstrate for the first time that MSX1 might play a substantial role in familial cases of hypodontia involving only second premolars and third molars.
Previous studies have indicated that mutations in the homeobox gene MSX1, paired domain transcription factor PAX9, and EDA are associated with non-syndromic oligodontia.
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.
Multiple previous reports confirm that several missense alleles of MSX1 exhibit Mendelian inheritance of an oligodontia phenotype (agenesis of more than six secondary teeth besides third molars).
At present, the list of genes involved in human non-syndromic hypodontia includes not only those encoding a signaling molecule (TGFA) and transcription factors (MSX1 and PAX9) that play critical roles during early craniofacial development, but also genes coding for a protein involved in canonical Wnt signaling (AXIN2), and a transmembrane receptor of fibroblast growth factors (FGFR1).
Therefore, the identified 11-nucleotide deletion may decrease the expression level of the MSX1 protein, but the link with oligodontia needs further study.
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.