MMP20 active-site mutation in hypomaturation Amelogenesis Imperfecta
MMP20 active-site mutation in hypomaturation Amelogenesis Imperfecta
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DOI：
10.1177/154405910508401112
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发表时间：
2005-11-01
影响因子：
7.6
通讯作者：
Hart, TC
中科院分区：
文献类型：
--
作者：
Ozdemir, D;Hart, PS;Hart, TC
成釉不全症是一组影响釉质形成的临床和遗传异质性疾病。迄今为止，在各种类型的AI中已报道了4个基因的突变。在编码2种釉质蛋白酶，基质金属蛋白酶20（MMP 20）和激肽释放酶4（KLK 4）的基因中的突变已分别在分离常染色体隐性发育不足AI的单个家族中报道。为了确定这些基因的突变频率，我们分析了15例常染色体隐性发育不良AI的土耳其先证者的MMP 20和KLK 4基因突变。未发现KLK 4基因突变，在1个家系中发现1个新的MMP 20基因突变（g.16250T > A）。该错义突变将锌催化结构域的保守活性位点His226残基改变为Gln（p.H226Q）。酶谱分析表明，这种错义突变消除MMP 20蛋白水解活性。在其余14名先证者中未发现MMP 20突变，强调了发育不足型AI的遗传异质性。
The Amelogenesis Imperfecta (AI) are a group of clinically and genetically heterogeneous disorders that affect enamel formation. To date, mutations in 4 genes have been reported in various types of AI. Mutations in the genes encoding the 2 enamel proteases, matrix metalloproteinase 20 (MMP20) and kallikrein 4 (KLK4), have each been reported in a single family segregating autosomal-recessive hypomaturation AI. To determine the frequency of mutations in these genes, we analyzed 15 Turkish probands with autosomal-recessive hypomaturation AI for MMP20 and KLK4 gene mutations. No KLK4 mutations were found. A novel MMP20 mutation (g.16250T > A) was found in one family. This missense mutation changed the conserved active-site His226 residue of the zinc catalytic domain to Gln (p.H226Q). Zymogram analysis demonstrated that this missense mutation abolished MMP20 proteolytic activity. No MMP20 mutations were found in the remaining 14 probands, underscoring the genetic heterogeneity of hypomaturation AI.