Amelogenesis Imperfecta: Genotype-Phenotype Studies in 71 Families
Amelogenesis Imperfecta: Genotype-Phenotype Studies in 71 Families
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DOI：
10.1159/000324339
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发表时间：
2011-01-01
影响因子：
2.7
通讯作者：
Hart, Tom C.
中科院分区：
文献类型：
--
作者：
Wright, J. Timothy;Torain, Melody;Hart, Tom C.
牙釉质发生障碍（AI）代表影响牙釉质的质量和数量的遗传条件。已知六种基因导致AI（AMELX、ENAM、MMP 20、KLK 4、FAM 83 H和WDR 72）。我们的目的是确定不同的基因突变在一个大的AI人口的分布，并评估表型-基因型的关系。受影响和未受影响的家庭成员进行了评估的临床和放射学检查。使用从血液或唾液中获得的基因组DNA完成基因分型。共有494人入组，其中430人（224人受影响，202人未受影响，4人未确定）属于71个家庭，其条件与AI诊断一致。观察到不同的临床表型（即发育不良、钙化不足和发育不良）。基因分型显示所有6个候选基因的突变。在132名受影响的个人（59%）和26个家庭（37%）中进行了分子诊断。突变涉及12个FAM 83 H家族（46%）、6个AMELX家族（23%）、3个ENAM家族（11%）、2个KLK 4和MMP 20家族（各8%）和1个WDR 72突变家族（4%）。表型变异与等位基因FAM 83 H和AMELX突变相关。两个看似无关的家庭有相同的KLK 4突变。未识别出候选基因突变的受AI影响的家族可能存在传统基因测序无法识别的突变（例如外显子缺失），或者可能存在本研究未评价的启动子序列突变。然而，研究结果表明，仍有新的AI致病基因有待鉴定。版权所有（C）2011 S. Karger AG，巴塞尔
Amelogenesis imperfecta (AI) represents hereditary conditions affecting the quality and quantity of enamel. Six genes are known to cause AI (AMELX, ENAM, MMP20, KLK4, FAM83H, and WDR72). Our aim was to determine the distribution of different gene mutations in a large AI population and evaluate phenotype-genotype relationships. Affected and unaffected family members were evaluated clinically and radiographically by one examiner. Genotyping was completed using genomic DNA obtained from blood or saliva. A total of 494 individuals were enrolled, with 430 (224 affected, 202 unaffected, and 4 not definitive) belonging to 71 families with conditions consistent with the diagnosis of AI. Diverse clinical phenotypes were observed (i.e. hypoplastic, hypocalcified, and hypomaturation). Genotyping revealed mutations in all 6 candidate genes. A molecular diagnosis was made in 132 affected individuals (59%) and in 26 of the families (37%). Mutations involved 12 families with FAM83H (46%), 6 families with AMELX (23%), 3 families with ENAM (11%), 2 families with KLK4 and MMP20 (8% for each gene), and 1 family with a WDR72 mutation (4%). Phenotypic variants were associated with allelic FAM83H and AMELX mutations. Two seemingly unrelated families had the same KLK4 mutation. Families affected with AI where candidate gene mutations were not identified could have mutations not identifiable by traditional gene sequencing (e.g. exon deletion) or they could have promoter sequence mutations not evaluated in this study. However, the results suggest that there remain new AI causative genes to be identified. Copyright (C) 2011 S. Karger AG, Basel