A review on non-syndromic tooth agenesis associated with PAX9 mutations

Abstract

SummaryTooth agenesis in the reduction of tooth number which includes hypodontia, oligodontia and anodontia is caused by disturbances and gene mutations that occur during odontogenesis. To date, several genetic mutations that unlock the causes of non-syndromic tooth agenesis are being discovered; these have been associated with certain illnesses because tooth development involves the interaction of several genes for tooth epithelium and mesenchyme odontogenesis. Mutation of candidate genes PAX9 and MSX1 have been identified as the main causes of hypodontia and oligodontia; meanwhile, AXIN2 mutation is associated with anodontia. Previous study using animal models reported that PAX9-deficient knockout mice exhibit missing molars due to an arrest of tooth development at the bud stage. PAX9 frameshift, missense and nonsense mutations are reported to be responsible; however, the most severe condition showed by the phenotype is caused by haploinsufficiency. This suggests that PAX9 is dosage-sensitive. Understanding the mechanism of genetic mutations will benefit clinicians and human geneticists in future alternative treatment investigations.

Paired Box 9 (PAX9), the RNA polymerase II transcription factor, regulates human ribosome biogenesis and craniofacial development

“…PAX9 has an established role in craniofacial patterning in human populations [25]. Our discovery that PAX9 also has a role in ribosome biogenesis supports a link between these craniofacial phenotypes and ribosome biogenesis, as has been observed for other ribosomopathies [29,67,68].…”

“…controlling gene expression [15,16]. In humans, mutations in PAX9 cause tooth agenesis as well as hair loss ( [17][18][19][20][21][22][23][24] and reviewed in [25]). Indeed, PAX9 mutations are the most prevalent mutation in patients with nonsyndromic tooth agenesis (including oligodontia; [26]).…”

“…PAX9 belongs to a family of transcription factors that play key roles in organogenesis and neural crest cell development by controlling gene expression [ 15 , 16 ]. In humans, mutations in PAX9 cause tooth agenesis as well as hair loss ([ 17 – 24 ] and reviewed in [ 25 ]). Indeed, PAX9 mutations are the most prevalent mutation in patients with nonsyndromic tooth agenesis (including oligodontia; [ 26 ]).…”

KMT2C, a histone methyltransferase, is mutated in a family segregating non-syndromic primary failure of tooth eruption

“…No epidemiological studies have been performed to evaluate the prevalence of PFE 17 . Several genes have been identified that play a role in odontogenesis including PAX9 , MSX1 , PTH1R , and AXIN2 36–38 . Strong evidence exist that, in most of the cases, PFE is an autosomal dominant heterogeneous condition associated with mutations in PTH1R gene and the genes involved in activation of cAMP/PKA pathway in tooth eruption 39,40 .…”

Developmental Dental Anomalies of Primary and Permanent Dentition

“…It is the most common dental anomaly and is present in about 1/5th of the population. The prevalence of hypodontia is variable in different populations [34]. Females are more commonly affected than males.…”