Keywords
Agenesia dental; Mayas; Variación genética; AXIN2; PAX9; MSX1.
How to Cite
Abstract
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.
References
Chhabra N., Goswami M., Chhabra A. Genetic basis of dental agenesis--molecular genetics patterning clinical dentistry. Med Oral Patol Oral Cir Bucal. 2014; 19 (2): 112-9.
Meade M.J., Dreyer C.W. Tooth agenesis: an overview of diagnosis, aetiology and management. Jpn Dent Sci Rev. 2023; 59 (1): 209-18.
Polder B.J., Van’t Hof M.A., Van Der Linden F.P.G.M., Kuijpers-Jagtman A.M. A meta-analysis of the prevalence of dental agenesis of permanent teeth. Community Dent Oral Epidemiol. 2004; 32 (3): 217-26.
Haddaji Mastouri M., De Coster P., Zaghabani A., Jammali F., Raouahi N., Ben Salem A., et al. Genetic study of non-syndromic tooth agenesis through the screening of paired box 9, msh homeobox 1, axin 2, and Wnt family member 10A genes: a case-series. Eur J Oral Sci. 2018; 126 (1): 24-32.
Yu M., Wong S.W., Han D., Cai T. Genetic analysis: Wnt and other pathways in nonsyndromic tooth agenesis. Oral Dis. 2019; 25 (3): 646-51.
Wong S.-W., Liu H-C.C., Han D., Chang H-G.G., Zhao H-S.S., Wang Y-X.X., et al. A novel non-stop mutation in MSX1 causing autosomal dominant non-syndromic oligodontia. Mutagenesis. 2014; 29 (5): 319-23.
Bonczek O., Balcar V.J., Šerý O. PAX9 gene mutations and tooth agenesis: a review. Clin Genet. 2017; 92 (5): 467-76.
Wong S., Han D., Zhang H., Liu Y., Zhang X., Miao M.Z., et al. Nine novel PAX9 mutations and a distinct tooth agenesis genotype-phenotype. J Dent Res. 2018; 97 (2): 155-62.
Šerý O., Bonczek O., Hloušková A., Černochová P., Vaněk J., Míšek I., et al. A screen of a large Czech cohort of oligodontia patients implicates a novel mutation in the PAX9 gene. Eur J Oral Sci. 2015; 123 (2): 65-71.
Shahid M., Balto H.A., Al-Hammad N., Joshi S., Khalil H.S., Somily A.M., et al. Mutations in MSX1, PAX9 and MMP20 genes in Saudi Arabian patients with tooth agenesis. Eur J Med Genet. 2016; 59 (8): 377-85.
Yamaguchi S., Machida J., Kamamoto M., Kimura M., Shibata A., Tatematsu T., et al. Characterization of novel MSX1 mutations identified in Japanese patients with nonsyndromic tooth agenesis. PLoS One. 2014; 9 (8): e102944.
Lammi L., Arte S., Somer M., Järvinen H., Lahermo P., Thesleff I., et al. Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am J Hum Genet. 2004; 74 (5): 1043-50.
Mu Y.D., Xu Z., Contreras C.I., McDaniel J.S., Donly K.J., Chen S. Mutational analysis of AXIN2, MSX1, and PAX9 in two Mexican oligodontia families. Genet Mol Res. 2013; 12 (4): 4446.
Herrera-Atoche J.R., Diaz-Morales S., Colome-Ruiz G., Escoffie-Ramirez M., Orellana M.F. Prevalence of dental anomalies in a Mexican population. Dent 3000. 2014; 2 (1): 7326061.
Silva-Zolezzi I., Hidalgo-Miranda A., Estrada-Gil J., Fernandez-Lopez J.C., Uribe-Figueroa L., Contreras A., et al. Analysis of genomic diversity in Mexican Mestizo populations to develop genomic medicine in Mexico. Proc Natl Acad Sci U S A. 2009; 106 (21): 8611-6.
González-Herrera L., Sosa-Escalante J.E., López-González P., López-González M.J., Gamboa-Magaña R.Y., Herrera-Diaz R.G., et al. Ancestral proportions based on 22 autosomal STRs of an admixed population (Mestizos) from the Península of Yucatán, México. Forensic Sci Int Genet Suppl Ser. 2019; 7 (1): 429-31.
Lara-Riegos J., Barquera R., Castillo-Chávez O. del, Medina-Escobedo C.E., Hernández-Zaragoza D.I., Arrieta-Bolaños E., et al. Genetic diversity of HLA system in two populations from Yucatán, Mexico: Mérida and rural Yucatán. Hum Immunol. 2020; 81 (9): 569-72.
Paixão-Côrtes V.R., Braga T., Salzano F.M., Mundstock K., Mundstock C.A., Bortolini M.C. PAX9 and MSX1 transcription factor genes in non-syndromic dental agenesis. Arch Oral Biol. 2011; 56 (4): 337-44.
Richards S., Aziz N., Bale S., Bick D., Das S., Gastier-Foster J., et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015; 17 (5):.405-24.
Noroozi N., Dastgheib S.A., Lookzadeh M.H., Mirjalili S.R., Noorishadkam M., Akbarian-Bafghi M.J., et al. Association of axis inhibition protein 2 polymorphisms with non-syndromic cleft lip with or without cleft palate in Iranian children. Fetal Pediatr Pathol. 2020; 39 (1): 29-37.
Rosales-Reynoso M.A., Arredondo-Valdez A.R., Wence-Chávez L.I., Barros-Núñez P., Gallegos-Arreola M.P., Flores-Martínez S.E., et al. AXIN2 polymorphisms and their association with colorectal cancer in Mexican Patients. Genet Test Mol Biomarkers. 2016; 20 (8): 438-44.
Li X., Li Y., Liu G., Wu W. New insights of the correlation between AXIN2 polymorphism and cancer risk and susceptibility: evidence from 72 studies. BMC Cancer. 2021; 21 (1): 353.
Liu H., Ding T., Zhan Y., Feng H. A novel AXIN2 missense mutation is associated with non-syndromic oligodontia. PLoS One. 2015; 10 (9): e0138221.
Wong, Liu H., Bai B., Chang H., Zhao H., Wang Y., et al. Novel missense mutations in the AXIN2 gene associated with non-syndromic oligodontia. Arch Oral Biol. 2014; 59 (3): 349-53.
Bergendal B., Klar J., Stecksén-Blicks C., Norderyd J., Dahl N. Isolated oligodontia associated with mutations in EDARADD, AXIN2, MSX1, and PAX9 genes. Am J Med Genet A. 2011; 155A (7): 1616-22.
Wang J., Xu Y., Chen J., Wang F., Huang R., Wu S., et al. PAX9 polymorphism and susceptibility to sporadic non-syndromic severe anodontia: a case-control study in southwest China. J Appl oral Sci. 2013; 21 (3): 256-64.
Vitria E.E., Tofani I., Kusdhany L., Bachtiar E.W. Genotyping analysis of the Pax9 gene in patients with maxillary canine impaction. F1000Res. 2019; 8 (1): 254.
Wang J., Jian F., Chen J., Wang H., Lin Y., Yang Z., et al. Sequence analysis of PAX9, MSX1 and AXIN2 genes in a Chinese oligodontia family. Arch Oral Biol. 2011; 56 (10): 1027-34.
Pereira T.V., Salzano F.M., Mostowska A., Trzeciak W.H., Ruiz-Linares A., Chies J.A.B., et al. Natural selection and molecular evolution in primate PAX9 gene, a major determinant of tooth development. Proc Natl Acad Sci U S A. 2006; 103 (15): 5676-81.
Ren J., Gan S., Zheng S., Li M., An Y., Yuan S., et al. Genotype-phenotype pattern analysis of pathogenic PAX9 variants in Chinese Han families with non-syndromic oligodontia. Front Genet. 2023; 14 (1): 1142776.
Matalova E., Fleischmannova J., Sharpe P.T., Tucker A.S. Tooth agenesis: from molecular genetics to molecular dentistry. J Dent Res. 2008; 87 (7): 617-23.
Mostowska A., Biedziak B., Jagodzinski P.P. Novel MSX1 mutation in a family with autosomal-dominant hypodontia of second premolars and third molars. Arch Oral Biol. 2012; 57 (6): 790-5.
Xuan K., Jin F., Liu Y.L., Yuan L.T., Wen L.Y., Yang F.S., et al. Identification of a novel missense mutation of MSX1 gene in Chinese family with autosomal-dominant oligodontia. Arch Oral Biol. 2008; 53 (8): 773-9.
Lidral A.C., Reising B.C. The role of MSX1 in human tooth agenesis. J Dent Res. 2002; 81 (4): 274-8.
Safari S., Ebadifar A., Najmabadi H., Kamali K., Abedini S.S. Screening PAX9, MSX1 and WNT10A mutations in 4 Iranian families with non-syndromic tooth agenesis. Avicenna J Med Biotechnol. 2020; 12 (4): 236.
Gao Y., Jiang X., Wei Z., Long H., Lai W. The EDA/EDAR/NF-κB pathway in non-syndromic tooth agenesis: A genetic perspective. Front Genet. 2023; 14 (1): 1168538.
Lee S., Ahn H., Kim H., Lee K., Kim S., Lee J.H. Identification of potential key variants in mandibular premolar hypodontia through whole-exome sequencing. Front Genet. 2023; 14 (1): 1248326.