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The present study aimed to determine the genetic variants of PAX9, MSX1, and AXIN2 in Mayan probands with non-syndromic dental agenesis (NSDA) from Yucatan, Mexico. We sequenced DNA of specific exons of the PAX9, MSX1, and AXIN2 genes by using the Sanger method in seven Mayan probands with familial NSDA attending orthodontic clinics in Merida, Yucatan, Mexico. We bioinformatically analyzed four genomes of unaffected people with Mayan ancestry for comparative purposes. Two Mayan probands had oligodontia (14 or 16 missing teeth) and five had hypodontia (1-2 missing teeth). We found the following genetic variants: rs8670 in MSX1; rs12881240 and rs4904210 in PAX9; and rs1060502133, rs1060502139, rs147716924, rs1330822418, rs769741903, rs9915936, rs1133683, and rs1234437759 in AXIN2. The genetic variants in PAX9, MSX1, and AXIN2 in Mayan probands with familial NSDA were benign and have previously been reported. In conclusion, the AXIN2 gene exhibited the highest number of known variants. Because some variants were also present in the genomes of unaffected people, additional functional and epidemiological studies are required to address their clinical significance and associated phenotypes., Este trabajo tuvo el objetivo de determinar las variantes genéticas de PAX9, MSX1 y AXIN2 en probandos mayas con agenesia dental no sindrómica (ADNS) de Yucatán, México. Se realizó secuenciación tipo Sanger del ADN de exones específicos de PAX9, MSX1 y AXIN2 en siete probandos Mayas con ADNS familiar atentidos en clínicas ortodónticas de Mérida, Yucatán, México. Se analizaron cuatro genomas de personas sanas con propósitos de comparación. Dos probandos Mayas fueron diagnosticados con oligodoncia (14 y 16 dientes perdidos) y cinco con hipodoncia (1-2 dientes perdidos). Se detectó la variante genética rs8670 en MSX1; PAX9 presentó rs12881249 y rs4904210; en AXIN2 se encontraron rs1060502133, rs1060502139, rs147716924, rs1330822418, rs769741903, rs9915936, rs1133683 y rs1234437759. Las variantes detectadas en PAX9, MSX1 y AXIN2 se clasificaron como benignas y ya habían sido previamente reportadas. En conclusión, el gen AXIN2 exhibió el mayor número de variantes. Ya que algunas de ellas también estuvieron presentes en genomas de personas sanas, se requieren estudios funcionales y epidemiológicos adicionales para determinar la significancia clínica de las variantes encontradas y los fenotipos asociados.

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 “ghost 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.

The correct formation of the aortic arch arteries depends on a coordinated and regulated gene expression profile within the tissues of the pharyngeal arches. Perturbation of the gene regulatory networks in these tissues results in congenital heart defects affecting the arch arteries and the outflow tract of the heart. Aberrant development of these structures leads to interruption of the aortic arch and double outlet right ventricle, abnormalities that are a leading cause of morbidity in 22q11 Deletion Syndrome (DS) patients. We have recently shown that Pax9 functionally interacts with the 22q11DS gene Tbx1 in the pharyngeal endoderm for 4th pharyngeal arch artery morphogenesis, with double heterozygous mice dying at birth with interrupted aortic arch. Mice lacking Pax9 die perinatally with complex cardiovascular defects and in this study we sought to validate further potential genetic interacting partners of Pax9, focussing on Gbx2 which is down-regulated in the pharyngeal endoderm of Pax9-null embryos. Here, we describe the Gbx2-null cardiovascular phenotype and demonstrate a genetic interaction between Gbx2 and Pax9 in the pharyngeal endoderm during cardiovascular development.