ENAM Mutations in Autosomal-dominant Amelogenesis Imperfecta

Abstract

To date, 4 unique enamelin gene (ENAM) defects have been identified in kindreds with amelogenesis imperfecta. To improve our understanding of the roles of enamelin in normal enamel formation, and to gain information related to possible genotype/phenotype correlations, we have identified 2 ENAM mutations in kindreds with hypoplastic ADAI, 1 novel (g.4806A>C, IVS6-2A>C) and 1 previously identified (g.8344delG), and have characterized the resulting enamel phenotypes. The IVS6-2A>C mutation caused a severe enamel phenotype in the proband, exhibiting horizontal grooves of severely hypoplastic enamel. The affected mother had several shallow hypoplastic horizontal grooves in the lower anterior teeth. In the case of the g.8344delG mutation, the phenotype was generalized hypoplastic enamel with shallow horizontal grooves in the middle 1/3 of the anterior teeth. In general, mutations in the human enamelin gene cause hypoplastic enamel, often with horizontal grooves, but the severity of the enamel defects is variable, even among individuals with the same mutation.

Novel WDR72 Mutation and Cytoplasmic Localization

“…We have now identified two AMELX (Kim et al, 2004), two ENAM (Kim et al, 2005a(Kim et al, , 2006, one MMP20 (Kim et al, 2005b), five FAM83H Ding et al, 2009), and one WDR72 mutation in this group, bringing to 12 the number of families having the genetic etiology of their AI determined. None of the 24 families had a KLK4 mutation.…”

Enamel Protein Regulation and Dental and Periodontal Physiopathology in Msx2 Mutant Mice

“…Some cracks were observed in this thin enamel layer. Various genetic forms of amelogenesis imperfecta 45 are secondary to mutations in human genes (enamelin, 46 kallikrein 4, 47 and enamelysin 48 ) and transgenic mouse lines. 23,25,49 -52 Among these clinical disorders and experimental models, the enamels of Msx2 Ϫ/Ϫ and amelogenin Ϫ/Ϫ mice harbor the most significant similarities, both corresponding to hypoplastic type of enamel defects.…”

The Importance of Serine Phosphorylation of Ameloblastin on Enamel Formation

“…In humans, the hypomineralization or hypoplastic classes of amelogenesis imperfecta have been related to mutations in the following genes: AMELX (Hart et al 2002;Kim et al 2004;Stephanopoulos et al 2005;Urzúa et al 2011), ENAM (Hart et al 2003;Hu and Yamakoshi 2003;Kim et al 2005;Stephanopoulos et al 2005), and recently AMBN (Poulter et al 2014). The mouse model in which exons 5 and 6 are deleted from Ambn showed severe hypoplastic amelogenesis imperfecta that had no enamel formation on the tooth surface (Fukumoto et al the genuine casein kinase phosphorylating secretory calcium-binding phosphoproteins (Ishikawa et al 2012;Tagliabracci et al 2012).…”