Amelogenesis imperfecta (AI) is a genetically and phenotypically heterogeneous genetic disorder affecting tooth enamel without other non-oral syndromic conditions. Based on a review of the literature, the authors constructed a candidate-gene-based mutational analysis strategy. To test the strategy, they identified two Turkish families with hypoplastic enamel without any other non-oral syndromic phenotype. The authors analyzed all exons and exon/intron boundaries of the enamelin (ENAM) gene for family 1 and the DLX3 and ENAM genes for family 2, to identify the underlying genetic etiology. The analysis revealed 2 ENAM mutations (autosomal-dominant g.14917delT and autosomal-recessive g.13185–13186insAG mutations). A single T deletion in exon 10 is a novel deletional mutation (g.14917delT, c.2991delT), which is predicted to result in a frameshift with a premature termination codon (p.L998fsX1062). This result supports the use of a candidate-gene-based strategy to study the genetic basis for AI.
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References
1.
Dong J, Amor D, Aldred MJ, Gu T, Escamilla M, MacDougall M (2005). DLX3 mutation associated with autosomal dominant amelogenesis imperfecta with taurodontism. Am J Med Genet A133:138–141.
2.
Gutierrez SJ, Chaves M, Torres DM, Briceno I (2007). Identification of a novel mutation in the enamelin gene in a family with autosomal-dominant amelogenesis imperfecta. Arch Oral Biol52:503–506.
3.
Hart PS, Michalec MD, Seow WK, Hart TC, Wright JT (2003). Identification of the enamelin (g.8344delG) mutation in a new kindred and presentation of a standardized ENAM nomenclature. Arch Oral Biol48: 589–596.
4.
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.
5.
Hart TC, Hart PS, Gorry MC, Michalec MD, Ryu OH, Uygur C, et al. (2003). Novel ENAM mutation responsible for autosomal recessive amelogenesis imperfecta and localised enamel defects. J Med Genet40:900–906.
6.
Hu JC, Simmer J (2007). Developmental biology and genetics of dental malformations. Orthod Craniofac Res10:45–52.
7.
Hu JC, Yamakoshi Y, Yamakoshi F, Krebsbach PH, Simmer JP (2005). Proteomics and genetics of dental enamel. Cells Tissues Organs181:219–231.
8.
Kida M, Ariga T, Shirakawa T, Oguchi H, Sakiyama Y (2002). Autosomal-dominant hypoplastic form of amelogenesis imperfecta caused by an enamelin gene mutation at the exon-intron boundary. J Dent Res81:738–742.
9.
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.
10.
Kim JW, Simmer JP, Hu YY, Lin BP, Boyd C, Wright JT, et al. (2004). Amelogenin p.M1T and p.W4S mutations underlying hypoplastic X-linked amelogenesis imperfecta. J Dent Res83:378–383.
11.
Kim JW, Seymen F, Lin BP, Kiziltan B, Gencay K, Simmer JP, et al. (2005a). ENAM mutations in autosomal-dominant amelogenesis imperfecta. J Dent Res84:278–282.
12.
Kim JW, Simmer JP, Hart TC, Hart PS, Ramaswami MD, Bartlett JD, et al. (2005b). MMP-20 mutation in autosomal recessive pigmented hypomaturation amelogenesis imperfecta. J Med Genet42:271–275.
13.
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.
14.
Kim JW, Lee SK, Lee ZH, Park JC, Lee KE, Lee MH, et al. (2008). FAM83H mutations in families with autosomal-dominant hypocalcified amelogenesis imperfecta. Am J Hum Genet82:489–494.
15.
Lee SK, Hu JC, Bartlett JD, Lee KE, Lin BP, Simmer JP, et al. (2008a). Mutational spectrum of FAM83H: the C-terminal portion is required for tooth enamel calcification. Hum Mutat29:E95–E99.
16.
Lee SK, Lee ZH, Lee SJ, Ahn BD, Kim YJ, Lee SH, et al. (2008b). DLX3 mutation in a new family and its phenotypic variations. J Dent Res87:354–357.
17.
Ozdemir D, Hart PS, Ryu OH, Choi SJ, Ozdemir-Karatas M, Firatli E, et al. (2005a). MMP20 active-site mutation in hypomaturation amelogenesis imperfecta. J Dent Res84:1031–1035.
18.
Ozdemir D, Hart PS, Firatli E, Aren G, Ryu OH, Hart TC (2005b). Phenotype of ENAM mutations is dosage-dependent. J Dent Res84:1036–1041.
19.
Papagerakis P, Lin HK, Lee KY, Hu Y, Simmer JP, Bartlett JD, et al. (2008). Premature stop codon in MMP20 causing amelogenesis imperfecta. J Dent Res87:56–59.
20.
Pavlic A, Petelin M, Battelino T (2007). Phenotype and enamel ultrastructure characteristics in patients with ENAM gene mutations g.13185–13186insAG and 8344delG. Arch Oral Biol52:209–217.
21.
Price JA, Wright JT, Kula K, Bowden DW, Hart TC (1998). A common DLX3 gene mutation is responsible for tricho-dento-osseous syndrome in Virginia and North Carolina families. J Med Genet35:825–828.
22.
Witkop CJ Jr (1988). Amelogenesis imperfecta, dentinogenesis imperfecta and dentin dysplasia revisited: problems in classification. J Oral Pathol17:547–553.
23.
Wright JT (2006). The molecular etiologies and associated phenotypes of amelogenesis imperfecta. Am J Med Genet A140:2547–2555.
24.
Wright JT, Kula K, Hall K, Simmons JH, Hart TC (1997). Analysis of the tricho-dento-osseous syndrome genotype and phenotype. Am J Med Genet72:197–204.
