Department of Cell and Developmental Biology, Dental Research Institute and BK21 Program, School of Dentistry, Seoul National University, 275-1 Yongon-dong, Chongno-gu, Seoul 110-768, Korea.
J Dent Res. 2010 Jan;89(1):46-50. doi: 10.1177/0022034509352844.
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.
蛋白水解酶在牙釉质形成过程中具有重要功能，而 Kallikrein 4（KLK4）和 enamelysin（MMP20）基因的突变会导致常染色体隐性遗传性牙釉质不全（ARAI）。到目前为止，仅在 ARAI 家系中报道了 1 种 KLK4 和 3 种 MMP20 突变。为了确定具有低成熟型牙釉质缺陷的家族中的 ARAI 是否是由编码牙釉质蛋白水解酶的基因的突变引起的，我们对候选基因进行了突变分析。突变和单倍型分析显示 MMP20 外显子 6 中存在导致 Hemopexin 结构域中单个氨基酸取代的 ARAI 致病点突变（c.910G>A，p.A304T）。Western blot 分析显示突变蛋白的表达减少，但酶谱分析表明该突变是一种功能性蛋白。先证者和受影响的兄弟均为该突变的纯合子，而未受影响的父母均为携带者。新萌出牙的牙釉质厚度正常，但呈粉笔白色，随着年龄的增长变得更暗。
