Role of genes in oro-dental diseases

Abstract

In oral cavity, the spectrum of diseases due to genetic alterations ranges from developmental disturbances of teeth to the pre-cancerous and cancerous lesions. Of late, significant progress has been made in the molecular analysis of tumors. With molecular genetic testing emerging as diagnostic, prognostic, and therapeutic approach, a review of genetic alterations ranging from the development of oro-facial structures to the tumors in the head and neck region are addressed in this article. The functional regulatory aspect of genes in relation to oro-facial structures are discussed separately, i.e., in relation to tooth genesis, tooth agenesis (non-syndromic, syndromic), tooth structural alterations, syndromic oro-facial defects, bone diseases, skin diseases (genodermatoses), and malignant tumors. In this literature, various genes involved in the development of the oro-facial structures and tooth in particular are discussed. The genetic basis of disorders in the tooth development (agenesis, hypodontia), tooth structural defects like amelogenesis imperfecta (AI), dentinogenesis imperfecta (DI), and oro-facial structural alterations (various syndromes) are explained.

GREM2 nucleotide variants and the risk of tooth agenesis

“…To date, only mutations in the MSX1 and PAX9 genes seem to be tooth‐type specific. The phenotype–genotype correlation analyses demonstrated that the MSX1 mutations are associated with hypodontia that predominantly affects second premolars and third molars, whereas mutations in PAX9 lead to agenesis of most molars, which can sometimes be combined with the absence of other teeth, including second premolars (Kavitha, Priyadharshini, Sivapathasundharam, & Saraswathi, ; Matalova, Fleischmannova, Sharpe, & Tucker, ).…”

Novel PAX9 mutation associated with syndromic tooth agenesis

“…These nucleotide variations, regardless of the pathogenic mechanism(s) involved, probably lead to inactivation of one PAX9 gene allele, suggesting haploinsufficiency as the potential underlying cause of tooth agenesis in affected individuals. It has been shown that a reduced amount of the PAX9 protein specifically affects molar development (7,15). However, the specific pattern of tooth agenesis associated with PAX9 mutations has not been Table 2 Paired box 9 (PAX9) mutations identified in patients with permanent tooth agenesis UTR, untranslated region.…”

“…At this critical stage of odontogenesis, Pax9 is required to maintain the mesenchymal expression of bone morphogenetic protein 4 ( Bmp4 ), which is involved in the induction of the epithelial signalling centre for tooth morphogenesis (enamel knot) . Analysis of human phenotypes revealed that PAX9 mutations are dominantly associated with the absence of most molars, which can sometimes be combined with the absence of second premolars and some of the incisors . Common PAX9 polymorphisms have been shown to be significantly correlated with hypodontia, including third‐molar agenesis, as well as with the crown size and shape of permanent teeth in East Asian populations .…”

Dental Approach to Craniofacial Syndromes: How Can Developmental Fields Show Us a New Way to Understand Pathogenesis?

“…Craniofacial research is currently focused especially on determination of genotypes of different syndromes [6, 18–21]. …”