The molecular etiologies and associated phenotypes of amelogenesis imperfecta

Abstract

The amelogenesis imperfectas (AIs) are a clinically and genetically diverse group of conditions that are caused by mutations in a variety of genes that are critical for normal enamel formation. To date, mutations have been identified in four genes (AMELX, ENAM, KLK4, MMP20) known to be involved in enamel formation. Additional yet to be identified genes also are implicated in the etiology of AI based on linkage studies. The diverse and often unique phenotypes resulting from the different allelic and non-allelic mutations in these genes provide an opportunity to better understand the role of these genes and their related proteins in enamel formation. Understanding the AI phenotypes also provides an aid to clinicians in directing molecular studies aimed at delineating the genetic basis underlying these diverse clinical conditions. Our current knowledge of the known mutations and associated phenotypes of the different AI subtypes are reviewed.

Fig. 1

Loss of amelogenin due to signal peptide mutations results in a marked reduction in enamel thickness as seen in this male with a p.M1T mutation. The teeth are relatively normal in color and slightly reduced in size and the extremely thin enamel can be more readily visualized on the dental radiographs [Kim et al., 2004]. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Fig. 2

Point AMELX mutations altering the tyrosine rich region of the amelogenin protein cause hypomaturation of the enamel producing the characteristic white cervical opaque and coronal brown discoloration of the enamel, as seen in this male with a P70T mutation. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Fig. 3

AMELX mutations affecting the C-terminus of the amelogenin protein cause a marked generalized decrease in enamel thickness in males (A) and produces vertical grooves in females due to Lyonization, as seen in the dentition of this heterozygous female (B). [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Fig. 4

Autosomal dominant ENAM mutations associated with haploinsufficiency produce a local hypoplastic phenotype characterized by horizontal bands of pits that occur at the same height on the crowns of all teeth despite their marked difference in chronological development as seen in the teeth of this affected individual [Mardh et al., 2002]. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Fig. 5

The generalized thin enamel in this affected individual has a rough pitted surface that results from an ENAM mutation producing a dominant negative affect. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Fig. 6

The autosomal recessive pigmented hypomaturation phenotype produced by a MMP20 mutation characterized by teeth that have reduced mineral content and have a white-to-brown discoloration [Kim et al., 2005b]. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Fig. 7

Autosomal recessive pigmented hypomaturation resulting from a KLK4 mutation is characterized by enamel of normal thickness that has a marked orange–brown discoloration, as seen in this affected female. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]