MMP20 Hemopexin Domain Mutation in Amelogenesis Imperfecta

Abstract

Proteolytic enzymes serve important functions during dental enamel formation, and mutations in the kallikrein 4 (KLK4) and enamelysin (MMP20) genes cause autosomal-recessive amelogenesis imperfecta (ARAI). So far, only 1 KLK4 and 3 MMP20 mutations have been reported in ARAI kindreds. To determine whether ARAI in a family with a hypomaturation-type enamel defect is caused by mutations in the genes encoding enamel proteolytic enzymes, we performed mutational analysis on candidate genes. Mutational and haplotype analyses revealed an ARAI-causing point mutation (c.910G>A, p.A304T) in exon 6 of MMP20 that results in a single amino acid substitution in the hemopexin domain. Western blot analysis showed decreased expression of the mutant protein, but zymogram analysis demonstrated that this mutant was a functional protein.The proband and an affected brother were homozygous for the mutation, and both unaffected parents were carriers. The enamel of newly erupted teeth had normal thickness, but was chalky white and became darker with age.

MMP20 Cleaves E-Cadherin and Influences Ameloblast Development

“…MMP20 is required for healthy dental enamel development. People and mice with homozygous MMP20 mutations have soft discolored enamel that may be hypoplastic and that easily abrades from the dentin surface [Caterina et al, 2002;Bartlett et al, 2004;Kim et al, 2005;Ozdemir et al, 2005; Bartlett et al, 2006;Papagerakis et al, 2008;Lee et al, 2010]. Herein we demonstrate that Mmp20 -null mouse ameloblasts improperly progress through the secretory stage of development and that MMP20 cleaves the E-cadherin extracellular domain.…”

Expression of Matrix Metalloproteinase (MMP)-20 and Potential Interaction with Dentin Sialophosphoprotein (DSPP) in Human Major Salivary Glands

“…A homozygous MMP-20 mutation in human and mice results in hypoplastic and discolored enamel that easily flakes off from the underlying dentin (Bartlett et al 2004;Bartlett et al 2006;Caterina 580817J HCXXX10.1369/0022155415580817Koli et alMMP-20 Expression in Human Major Salivary Glands research-article2015 et al 2002;Kim et al 2005;Ozdemir et al 2005;Papagerakis et al 2008;Lee et al 2010).…”

Why Does Enamel in <i>Klk4</i>-Null Mice Break above the Dentino-Enamel Junction?

“…Mutations in MMP20 [Kim et al, 2005;Ozdemir et al, 2005;Papagerakis et al, 2008;Lee et al, 2010] and KLK4 [Hart et al, 2004] cause autosomal recessive amelogenesis imperfecta (MIM ID No. 612529 and No.…”