Novel PAX9 Mutations Causing Isolated Oligodontia

TL;DR

This study finds new mutations in the PAX9 gene that cause a rare tooth development disorder called oligodontia.

Contribution

The study identifies two novel PAX9 mutations and shows that a silent mutation affects RNA splicing, contributing to oligodontia.

Findings

Two novel PAX9 mutations were identified in families with non-syndromic oligodontia.

A silent mutation in PAX9 causes aberrant pre-mRNA splicing, leading to altered splicing products.

The study strengthens the diagnostic understanding of PAX9-related oligodontia.

Abstract

Hypodontia, i.e., missing one or more teeth, is a relatively common human disease; however, oligodontia, i.e., missing six or more teeth, excluding the third molars, is a rare congenital disorder. Many genes have been shown to cause oligodontia in non-syndromic or syndromic conditions. In this study, we identified two novel PAX9 mutations in two non-syndromic oligodontia families. A mutational analysis identified a silent mutation (NM_006194.4: c.771G>A, p.(Gln257=)) in family 1 and a frameshift mutation caused by a single nucleotide duplication (c.637dup, p.(Asp213Glyfs*104)) in family 2. A minigene splicing assay revealed that the silent mutation resulted in aberrant pre-mRNA splicing instead of normal splicing. The altered splicing products are ones with an exon 4 deletion or using a cryptic 5’ splicing site in exon 4. Mutational effects were further investigated using protein expression, luciferase activity assay and immunolocalization. We believe this study will not only expand the mutational spectrum of PAX9 mutations in oligodontia but also strengthen the diagnostic power related to the identified silent mutation.

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