A novel PITX2 mutation in non-syndromic oro-dental anomalies

Abstract

Objective

To identify oro-dental characteristics and genetic etiology of a family affected with non-syndromic oro-dental anomalies.

Subjects and methods

Physical and oral features were characterised. DNA was collected from an affected Thai family. Whole exome sequencing was employed to identify the pathogenic variants associated with inherited oro-dental anomalies. The presence of the identified mutation was confirmed by Sanger sequencing.

Results

We observed unique oro-dental manifestations including oligodontia, retained primary teeth, taurodont molars, peg-shaped maxillary central incisors, high attached frenum with nodule, and midline diastema in the proband and her mother. Mutation analyses revealed a novel heterozygous frameshift deletion, c.573_574delCA, p.L193QfsX5, in exon 5 of PITX2A in affected family members. The amino acid alterations, localised in the transcriptional activation domain 2 in the C terminus of PITX2, were evolutionarily conserved. Mutations in PITX2 have been associated with autosomal-dominant Axenfeld-Rieger syndrome and non-syndromic eye abnormalities, but never been found to cause isolated oral anomalies.

Conclusions

This study for the first time demonstrates that the PITX2 mutation could lead to non-syndromic oro-dental anomalies in humans. We propose that the specific location in the C-terminal domain of PITX2 is exclusively necessary for tooth development.

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