Although our results are consistent with a lack of association of MSX1rs12532 and the risk of unilateral NSCLP and tooth agenesis, further studies with additional SNPs and a more diverse ethnic cohort are warranted.
Heterozygous mutations in AXIN2 have been shown to cause ectodermal dysplasia (including tooth agenesis, or more specifically, oligodontia), and, in some carriers, colorectal cancer and/or adenomatous polyposis develops.
The WNT10A gene has been confirmed as the second molecular candidate that has been identified and accounts for one-half of non-EDA patients and one-third of NSTA patients.
The variant genotype of the MSX1rs8670 SNP was the most frequent in frontal agenesis; meanwhile in the lateral agenesis NSH group, the AXIN2 rs2240308 SNP showed a higher frequency of the variant genotype, with a trend towards statistical significance.
Despite significant progress in the genetics of tooth agenesis, many gaps in knowledge exist in refining the genotype-phenotype correlation between PAX9 and tooth agenesis.
Based on previous in vitro experiments on mutation disrupting function of Msx1 homeodomain, we assume that the heterozygous g.8177G>T nonsense mutation affects the amount and function of Msx1 protein and leads to tooth agenesis.
WNT10A has previously been associated with both syndromic and non-syndromic forms of tooth agenesis, and this report further expands our knowledge of genetic variation underlying non-syndromic forms of this condition.
Novel homozygous and heterozygous variants in LRP6, DKK1, LAMA3, and COL17A1 genes, as well as known variants in WNT10A, were identified as likely pathogenic in isolated tooth agenesis.
Mutations in GATA6 should be strongly considered in cases of diabetes due to pancreatic hypoplasia or agenesis, and potentially affected family members should be tested regardless of phenotype.
We conclude that this frameshift mutation in the homeodomain (which plays an essential role in DNA binding) of MSX1 gene is responsible for tooth agenesis in this family.
We also report here a novel Glu78FS MSX1 mutation in one family segregating an autosomal dominant form of severe tooth agenesis as an illustration of an evolving theme, i.e., different mutations in the same gene can result in a spectrum of dentofacial phenotypic severity.
Transcription factors PAX9 and MSX1 play crucial roles in the development of permanent teeth at the bud stage, and their loss-of-function variants have been associated with congenital tooth agenesis.