The aim of the present study was to characterize the phenotype and to verify sequence variations in the LGR5 gene in a Brazilian family with ankyloglossia associated with tooth number anomalies.
Moreover, EMSA and ChIP assays demonstrated that the allele A disrupts the binding site of ETS-1, thus markedly decreases the activity of the TBX22 promoter, which is likely to lead to the birth defect of the CPO without ankyloglossia.
X-linked cleft palate (CPX) is caused by mutations in the gene encoding the TBX22 transcription factor and is known to exhibit phenotypic variability, usually involving either a complete, partial or submucous cleft palate, with or without ankyloglossia.
Our study has demonstrated that TBX22 mutation is associated not only with cleft palate and ankyloglossia, but also cleft lip and palate and tooth agenesis.
Mutations in the coding region of the TBX22 gene are not a major cause of ankyloglossia in the Finnish population and do not explain the sex difference or inheritance of tongue-tie.
Here, we report a Tbx22(null) mouse, which has a submucous cleft palate (SMCP) and ankyloglossia, similar to the human phenotype, with a small minority showing overt clefts.
The T-box transcription factor TBX22 is essential for normal craniofacial development, as demonstrated by the finding of nonsense, frameshift, splice-site, or missense mutations in patients with X-linked cleft palate (CPX) and ankyloglossia.
Recently, mutations in TBX22 were found to cause X-linked cleft palate (CPX and ankyloglossia), a semidominant X-linked disorder affecting formation of the secondary palate.
We describe TBX22 expression in early human development, where expression is found in the palatal shelves and is highest prior to elevation to a horizontal position above the tongue. mRNA is also detected in the base of the tongue in the region of the frenulum that corresponds to the ankyloglossia seen in CPX patients.