Familial oligodontia and regional odontodysplasia associated with a PAX9 initiation codon mutation

Abstract

Objective Tooth agenesis is one of the most common craniofacial developmental anomalies. In hypodontia, one to five teeth are missing, whereas oligodontia refers to the absence of at least six teeth, excluding the third molars. Mutations in several genes including MSX1, PAX9, AXIN2, and WNT10A have been shown to cause non-syndromic tooth agenesis. Regional odontodysplasia (RO), also known as Bghost teeth,^is a rare developmental anomaly of tooth formation affecting both dentitions. Some possible causes of RO have been suggested, yet the etiology remains unknown. Because the phenotypes of both oligodontia and RO co-occur in one Finnish family, the aim here was to investigate the genetic etiology of the two conditions. Materials and methods A mutation screening of the genes MSX1, PAX9, AXIN2, and WNT10A was performed for the family members of a RO patient and family history of oligodontia. Results An initiation codon mutation of the PAX9 gene was found in the proband and segregating with oligodontia in the family. Conclusions The etiology of regional odontodysplasia (RO) may be genetic and the same genes can be involved both in RO and tooth agenesis. Clinical relevance Our results give new insights into the etiology of regional odontodysplasia, yet further results are needed.

Functional study of novel PAX9 variants: The paired domain and non‐syndromic oligodontia

“…All identified variants resided within the PD, the DNA‐binding domain of PAX9, and were predicted to affect evolutionarily conserved amino acid residues. This distribution corresponds with the germline variant hot spot of PAX9 that correlated with NSO (Liang et al., 2016), considering that approximately half (26/53) of the PAX9 variants found in previous studies reside in the PD (Bonczek et al., 2017; Daw et al., 2017; Koskinen et al., 2019; Sarkar et al., 2017; Wong et al., 2018; Zhang et al., 2019). Since our results support the viewpoint that the evolutionarily conserved region closely interrelates with most of the variant hot spots, the PAX9 hot spot region can be prioritized for variant screening (Walker et al., 1999).…”

“…Although approximately 50 pathogenic variants have so far been identified in PAX9 that lead to NSO (Bonczek et al., 2017; Daw et al., 2017; Koskinen et al., 2019; Sarkar et al., 2017; Wong et al., 2018; Zhang et al., 2019), novel variants continue to be identified, and the definite pathogenic mechanism underlying PAX9‐ related NSO has not yet been elucidated. In this study, we sought to provide more evidence to address this important issue.…”

Clinical, Radiographic and Histologic Evaluation of Regional Odontodysplasia: an Unusual Case Report with 6-Year Follow-Up

“…Genetic testing of patients and exome/genome analysis is required to obtain more information on the aetiology of this rare abnormality. Other conditions that share some characteristics with regional odontodysplasia include dentin dysplasia type I and II, rickets, hypophosphatasia, amelogenesis imperfecta, and dentinogenesis imperfecta [11][12][13].…”

“…RO is not a hereditary condition but seems to be related to local factors during dental development. One theory suggests that it can be produced by a somatic mutation of the PAX9 gene occurring at an early stage of development, which may predispose the outgrowth of an anomaly such as regional odontodysplasia [11][12][13].…”

Two novel mutations in MSX1 causing oligodontia

“…Among those genes, NSTA is mostly associated with mutations in PAX9, MSX1, WNT10A, AXIN2 and EDA [28][29][30]. Therefore, in this study, we searched for mutations in the above five genes in two unrelated individuals with non-syndromic oligodontia.…”