Proteolytic enzymes are necessary for the mineralization of dental enamel during development, and mutations in the kallikrein 4 (KLK4) and enamelysin (MMP20) genes cause autosomal-recessive amelogenesis imperfecta (ARAI). So far, only one KLK4 and two MMP20 mutations have been reported. We have identified an ARAI-causing point mutation (c.102G>A, g.102G>A, and p.W34X) in exon 1 of MMP20 in a proband with autosomal-recessive hypoplastic-hypomaturation amelogenesis imperfecta. The G to A transition changes the tryptophan (W) codon (TGG) at amino acid position 34 into a translation termination (X) codon (TGA). No disease-causing sequence variations were detected in KLK4. The affected enamel is thin, with mild spacing in the anterior dentition. The enamel layer is hypomineralized, does not contrast with dentin on radiographs, and tends to chip away from the underlying dentin. An intrinsic yellowish pigmentation is evident, even during eruption. The phenotype supports current ideas concerning the function of enamelysin.
Get full access to this article
View all access options for this article.
References
1.
Bartlett JD, Simmer JP, Xue J, Margolis HC, Moreno EC -1996-. Molecular cloning and mRNA tissue distribution of a novel matrix metalloproteinase isolated from porcine enamel organ. Gene183:123–128.
2.
Bartlett JD, Beniash E, Lee DH, Smith CE -2004-. Decreased mineral content in MMP-20 null mouse enamel is prominent during the maturation stage. J Dent Res83:909–913.
3.
Bègue-Kirn C, Krebsbach PH, Bartlett JD, Butler WT -1998-. Dentin sialoprotein, dentin phosphoprotein, enamelysin and ameloblastin: tooth-specific molecules that are distinctively expressed during murine dental differentiation. Eur J Oral Sci106:963–970.
4.
Caterina JJ, Skobe Z, Shi J, Ding Y, Simmer JP, Birkedal-Hansen H, et al. -2002-. Enamelysin -matrix metalloproteinase 20--deficient mice display an amelogenesis imperfecta phenotype. J Biol Chem277:49598–49604.
5.
Daculsi G, Kerebel B -1978-. High-resolution electron microscope study of human enamel crystallites: size, shape, and growth. J Ultrastruct Res65:163–172.
6.
Fincham AG, Moradian-Oldak J, Simmer JP -1999-. The structural biology of the developing dental enamel matrix. J Struct Biol126:270–299.
7.
Fukae M, Tanabe T, Uchida T, Lee SK, Ryu OH, Murakami C, et al. -1998-. Enamelysin -matrix metalloproteinase-20-: localization in the developing tooth and effects of pH and calcium on amelogenin hydrolysis. J Dent Res77:1580–1588.
8.
Fukumoto S, Kiba T, Hall B, Iehara N, Nakamura T, Longenecker G, et al. -2004-. Ameloblastin is a cell adhesion molecule required for maintaining the differentiation state of ameloblasts. J Cell Biol167:973–983.
9.
Gibson CW, Yuan ZA, Hall B, Longenecker G, Chen E, Thyagarajan T, et al. -2001-. Amelogenin-deficient mice display an amelogenesis imperfecta phenotype. J Biol Chem276:31871–31875.
10.
Hart PS, Hart TC, Michalec MD, Ryu OH, Simmons D, Hong S, et al. -2004-. Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta. J Med Genet41:545–549.
11.
Hu JC, Simmer J -2007-. Developmental biology and genetics of dental malformations. Orthod Craniofac Res10:45–52.
12.
Hu JC, Ryu OH, Chen JJ, Uchida T, Wakida K, Murakami C, et al. -2000-. Localization of EMSP1 expression during tooth formation and cloning of mouse cDNA. J Dent Res79:70–76.
13.
Hu JC, Sun X, Zhang C, Liu S, Bartlett JD, Simmer JP -2002-. Enamelysin and kallikrein-4 mRNA expression in developing mouse molars. Eur J Oral Sci110:307–315.
14.
Iwata T, Yamakoshi Y, Hu JC, Ishikawa I, Bartlett JD, Krebsbach PH, et al. -2007-. Processing of ameloblastin by MMP-20. J Dent Res86:153–157.
15.
Kida M, Sakiyama Y, Matsuda A, Takabayashi S, Ochi H, Sekiguchi H, et al. -2007-. A novel missense mutation -p.P52R- in amelogenin gene causing X-linked amelogenesis imperfecta. J Dent Res86:69–72.
16.
Kim JW, Simmer JP, Hart TC, Hart PS, Ramaswami MD, Bartlett JD, et al. -2005-. MMP-20 mutation in autosomal recessive pigmented hypomaturation amelogenesis imperfecta. J Med Genet42:271–275.
17.
Kim JW, Simmer JP, Lin BP, Seymen F, Bartlett JD, Hu JC -2006-. Mutational analysis of candidate genes in 24 amelogenesis imperfecta families. Eur J Oral Sci114-Suppl 1-:3–12.
18.
Lammi L, Arte S, Somer M, Jarvinen H, Lahermo P, Thesleff I, et al. -2004-. Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am J Hum Genet74:1043–1050.
19.
Llano E, Pendas AM, Knauper V, Sorsa T, Salo T, Salido E, et al. -1997-. Identification and structural and functional characterization of human enamelysin -MMP-20-. Biochemistry36:15101–15108.
20.
Masuya H, Shimizu K, Sezutsu H, Sakuraba Y, Nagano J, Shimizu A, et al. -2005-. Enamelin -Enam- is essential for amelogenesis: ENU-induced mouse mutants as models for different clinical subtypes of human amelogenesis imperfecta -AI-. Hum Mol Genet14:575–583.
21.
Overall CM, Limeback H -1988-. Identification and characterization of enamel proteinases isolated from developing enamel. Amelogeninolytic serine proteinases are associated with enamel maturation in pig. Biochem J256:965–972.
22.
Ozdemir D, Hart PS, Firatli E, Aren G, Ryu OH, Hart TC -2005-. Phenotype of ENAM mutations is dosage-dependent. J Dent Res84:1036–1041.
23.
Ryu OH, Fincham AG, Hu CC, Zhang C, Qian Q, Bartlett JD, et al. -1999-. Characterization of recombinant pig enamelysin activity and cleavage of recombinant pig and mouse amelogenins. J Dent Res78:743–750.
24.
Ryu O, Hu JC, Yamakoshi Y, Villemain JL, Cao X, Zhang C, et al. -2002-. Porcine kallikrein-4 activation, glycosylation, activity, and expression in prokaryotic and eukaryotic hosts. Eur J Oral Sci110:358–365.
25.
Simmer JP, Hu JC -2002-. Expression, structure, and function of enamel proteinases. Connect Tissue Res43:441–449.
26.
Simmer JP, Fukae M, Tanabe T, Yamakoshi Y, Uchida T, Xue J, et al. -1998-. Purification, characterization, and cloning of enamel matrix serine proteinase 1. J Dent Res77:377–386.
27.
Simmer JP, Sun X, Yamada Y, Zhang CH, Bartlett JD, Hu JC-C -2004-. Enamelysin and kallikrein-4 expression in the mouse incisor. In: Biomineralization: formation, diversity, evolution and application. Proceedings of the 8th International Symposium on Biomineralization, Niigata, Japan, Sept. 25–28, 2001. Kobayashi I, Ozawa H, editors. Hadano, Japan: Tokai University Press, pp. 348–352.
28.
Smith CE -1998-. Cellular and chemical events during enamel maturation. Crit Rev Oral Biol Med9:128–161.
29.
Stockton DW, Das P, Goldenberg M, D’Souza RN, Patel PI -2000-. Mutation of PAX9 is associated with oligodontia. Nat Genet24:18–19.
30.
Tanabe T -1984-. Purification and characterization of proteolytic enzymes in porcine immature enamel. Tsurumi Shigaku10:443–452.
31.
Vastardis H, Karimbux N, Guthua SW, Seidman JG, Seidman CE -1996-. A human MSX1 homeodomain missense mutation causes selective tooth agenesis. Nat Genet13:417–421.
32.
Wagner E, Lykke-Andersen J -2002-. mRNA surveillance: the perfect persist. J Cell Sci115:3033–3038.
33.
Witkop CJ Jr -1988-. Amelogenesis imperfecta, dentinogenesis imperfecta and dentin dysplasia revisited: problems in classification. J Oral Pathol17:547–553.
34.
Witkop CJ Jr, Sauk JJ Jr -1977-. Heritable defects of enamel. In: Oral facial genetics. Stewart RE, Prescott GH, editors. St. Louis: C.V. Mosby Co., pp. 151–226.
35.
Yamada Y, Yamakoshi Y, Gerlach R, Hu C, Matsumoto K, Fukae M, et al. -2003-. Purification and characterization of enamelysin from secretory stage pig enamel. Arch Comp Biol Tooth Enam8:21–25.
