MSX1, PAX9, and TGFA Contribute to Tooth Agenesis in Humans

Abstract

In this study, we sought to determine the association between tooth agenesis and DNA sequence variation in the genes MSX1 and PAX9 in an ethnically diverse human population. Since cleft lip/palate is also associated with both tooth agenesis and the gene TGFA, we included TGFA in the analysis as well. Cheek swab samples were obtained for DNA analysis from 116 case/parent trios. Probands had at least one developmentally missing tooth, excluding third molars. Genotyping was performed by single-strand conformational polymorphism or kinetic polymerase chain-reaction assays. Transmission distortion of the marker alleles and DNA sequence analysis was performed. Results showed that tooth agenesis is associated with markers of the genes MSX1 and TGFA. No mutations were found in MSX1 or PAX9 coding regions. There were statistically significant data suggesting that MSX1 interacts with PAX9. These findings suggest that MSX1, PAX9, and TGFA play a role in isolated dental agenesis.

A study of patients attending a multidisciplinary hypodontia clinic over a five year period

“…[7][8][9] Various genes have been implicated, such as MSX, PAX9 and TGFA. [10][11][12][13][14][15] Management of hypodontia can be challenging as not only is this often complex but also various treatment options exist. Thus treatment planning may involve multiple dental disciplines and treatment phases.…”

Clinical and functional data implicate the Arg(151)Ser variant of MSX1 in familial hypodontia

“…Primers were used according to previous reports, 15,47 and were used to amplify all exons of the candidate genes by PCR from genomic DNA. The MSX1 gene consists of two exons separated by a 1.6-kb intron that has a polymorphic CA dinucleotide repeat within its boundaries.…”

Dentistry and Molecular Biology: A Promising Field for Tooth Agenesis Management

“…For example, in mice, MSX1 and PAX9 genes form an auto-regulatory gene network where PAX9 activation is required for completion of tooth development (Nieminen 2007). Evidence from human population studies has also shown that there is a similar molecular mechanism regulating odontogenesis (Vieira et al 2004).…”

“…However, there is no consensus among authors concerning the interaction between MSX1 and TGFA. Some studies show no statistically significant evidence of interaction between these genes in human tooth agenesis (Vieira et al 2004), whereas others indicate strong correlation (Jugessur et al 2003) among individuals with clefts.…”

“…Its main cause is related to abnormal function of specific genes which play key roles during odontogenesis, particularly MSX1 and PAX9. Hundreds of genes are known to be directly or indirectly involved in the regulation of tooth development, such as AXIN2, TGFA, IRF6, and FGFR1 (Vieira et al 2004;Peres et al 2005;Mostowska et al 2006;Vieira et al 2007), and defects in any of these genes can cause agenesis. However, mutations in MSX1 and PAX9 appear to be more critical, since they are much more prevalent among affected individuals when compared with individuals with tooth agenesis causally related to mutations in the other genes.…”