The Molecular Basis of Hereditary Enamel Defects in Humans

Abstract

The formation of human enamel is highly regulated at the molecular level and involves thousands of genes. Requisites for development of this highly mineralized tissue include cell differentiation; production of a unique extracellular matrix; processing of the extracellular matrix; altering of cell function during different stages of enamel formation; cell movement and attachment; regulation of ion and protein movement; and regulation of hydration, pH, and other conditions of the microenvironment, to name just a few. Not surprising, there is a plethora of hereditary conditions with an enamel phenotype. The objective of this review was to identify the hereditary conditions listed on Online Mendelian Inheritance in Man (OMIM) that have an associated enamel phenotype and whether a causative gene has been identified. The OMIM database was searched with the terms amelogenesis, enamel, dental, and tooth, and all results were screened by 2 individuals to determine if an enamel phenotype was identified. Gene and gene product function was reviewed on OMIM and from publications identified in PubMed. The search strategy revealed 91 conditions listed in OMIM as having an enamel phenotype, and of those, 71 have a known molecular etiology or linked genetic loci. The purported protein function of those conditions with a known genetic basis included enzymes, regulatory proteins, extracellular matrix proteins, transcription factors, and transmembrane proteins. The most common enamel phenotype was a deficient amount of enamel, or enamel hypoplasia, with hypomineralization defects being reported less frequently. Knowing these molecular defects allows an initial cataloging of molecular pathways that lead to hereditary enamel defects in humans. This knowledge provides insight into the diverse molecular pathways involved in enamel formation and can be useful when searching for the genetic etiology of hereditary conditions that involve enamel.

Amelogenesis imperfecta in familial hypomagnesaemia and hypercalciuria with nephrocalcinosis caused byCLDN19gene mutations

“…Moreover, in multiple cases, no mutations have been found in any of these genes, suggesting involvement of other genes in AI 35–38. Recently, Wright et al 39 performed a strategic search in OMIM and found 71 conditions having an enamel phenotype associated with a known molecular aetiology or linked genetic loci. Because of the absence of detailed information, most of the enamel defects reported could not be classified as AI.…”

Function and repair of dental enamel – Potential role of epithelial transport processes of ameloblasts

“…A number of recent studies revealed that mutations of multiple proteins could cause syndrome-associated and nonsyndromic enamel defects (for review see Refs. [11], but because of the space limitation the present work can discuss only the biomineralization process in general, and the contribution to this by amelogenin, the most abundant enamel protein.…”

Family-Based Genetic Association for Molar-Incisor Hypomineralization

“…The genetic control of dental development represents a complex series of events, and occasional mutations in the genes coding enamel proteins may cause alterations that affect the molecular pathways. The consequence is the occurrence of a deficiency in the amount of enamel (hypoplasia), a change in the composition (hypomineralization), or a change in the enamel structure [Wright et al, 2015]. Therefore, amelogenesis is under strict genetic control, and even caries susceptibility can be affected by genetic variation [Simmer and Hu, 2001;Deeley et al, 2008;Vieira et al, 2008;Shimizu et al, 2012].…”