Analyses of MMP20 Missense Mutations in Two Families with Hypomaturation Amelogenesis Imperfecta.
Analyses of MMP20 Missense Mutations in Two Families with Hypomaturation Amelogenesis Imperfecta.
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DOI：
10.3389/fphys.2017.00229
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发表时间：
2017
影响因子：
4
通讯作者：
Kim JW
中科院分区：
文献类型：
--
作者：
Kim YJ;Kang J;Seymen F;Koruyucu M;Gencay K;Shin TJ;Hyun HK;Lee ZH;Hu JC;Simmer JP;Kim JW
牙釉质形成障碍是一组罕见的遗传性疾病，影响牙釉质形成，定量和/或定性。本研究的目的是确定两个家族的遗传病因，提出了发育不良的釉质发育迟缓。从参与的家庭成员获得的外周血样品中分离DNA。使用来自两个先证者的DNA样品进行全外显子组测序。将测序数据与NCBI人参考基因组（NCBI build 37.2，hgl 9）比对，并用dbSNP build 138注释序列变异。在两个先证者中均发现MMP 20突变。一个纯合错义突变（c.678T>A; p.His226Gln）被确定在近亲家庭1。在非血缘家族2中鉴定出复合杂合MMP 20突变（c.540 T>A，p.Tyr180* 和c.389 C>T，p.Thr130 Ile）。家族1中受影响的人显示发育不足AI伴深棕色变色，这与先前报告中具有相同突变的临床表型相似。然而，家族2先证者的牙列显示出轻微的淡黄色变色，透明度降低。功能分析显示，p.Thr130Ile突变蛋白具有降低的MMP 20活性，而在家族1先证者中没有功能性MMP 20。这些结果扩大了MMP 20的突变谱，并拓宽了我们对釉质发生中基因型-表型相关性的理解。
Amelogenesis imperfecta is a group of rare inherited disorders that affect tooth enamel formation, quantitatively and/or qualitatively. The aim of this study was to identify the genetic etiologies of two families presenting with hypomaturation amelogenesis imperfecta. DNA was isolated from peripheral blood samples obtained from participating family members. Whole exome sequencing was performed using DNA samples from the two probands. Sequencing data was aligned to the NCBI human reference genome (NCBI build 37.2, hg19) and sequence variations were annotated with the dbSNP build 138. Mutations in MMP20 were identified in both probands. A homozygous missense mutation (c.678T>A; p.His226Gln) was identified in the consanguineous Family 1. Compound heterozygous MMP20 mutations (c.540T>A, p.Tyr180* and c.389C>T, p.Thr130Ile) were identified in the non-consanguineous Family 2. Affected persons in Family 1 showed hypomaturation AI with dark brown discoloration, which is similar to the clinical phenotype in a previous report with the same mutation. However, the dentition of the Family 2 proband exhibited slight yellowish discoloration with reduced transparency. Functional analysis showed that the p.Thr130Ile mutant protein had reduced activity of MMP20, while there was no functional MMP20 in the Family 1 proband. These results expand the mutational spectrum of the MMP20 and broaden our understanding of genotype-phenotype correlations in amelogenesis imperfecta.