Mutational spectrum of FAM83H: the C-terminal portion is required for tooth enamel calcification.
Mutational spectrum of FAM83H: the C-terminal portion is required for tooth enamel calcification.
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DOI：
10.1002/humu.20789
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发表时间：
2008-08
期刊：
影响因子：
3.9
通讯作者：
Kim, Jung-Wook
中科院分区：
文献类型：
--
作者：
Lee, Sook-Kyung;Hu, Jan C-C;Bartlett, John D;Lee, Kyung-Eun;Lin, Brent P-J;Simmer, James P;Kim, Jung-Wook
牙釉质的形成是通过特殊的细胞外基质蛋白的协同活动，包括amelogenin， enamelin， MMP20和KLK4。编码这些蛋白的基因缺陷导致非综合征性遗传性牙釉质畸形，统称为成釉发育不全症（AI）。然而，这些基因仅占所有人工智能案例的四分之一左右。最近，我们发现了FAM83H突变导致常染色体显性低钙化无淀粉性发育不全症（ADHCAI）。与其他导致AI的基因不同，FAM83H不编码细胞外基质蛋白。它在细胞内的位置和功能是完全未知的。我们在此报告了四种ADHCAI患者中新的FAM83H突变。最后一个外显子均为无义突变（c.1243G>T, p.E415X; c.891T>A, p.Y297X; c.1380G>A, p.W460X; c.2029C>T, p.p q677x）。这些突变从通常由1179个残基组成的蛋白质的c端删除了503到883个氨基酸。这些突变导致牙釉质层出现如此严重的缺陷而不影响身体其他部位的原因尚不清楚。然而，似乎很明显，蛋白质的大c端部分对于适当的牙釉质钙化是必不可少的。
Dental enamel forms through the concerted activities of specialized extracellular matrix proteins, including amelogenin, enamelin, MMP20, and KLK4. Defects in the genes encoding these proteins cause non-syndromic inherited enamel malformations collectively designated as amelogenesis imperfecta (AI). These genes, however, account for only about a quarter of all AI cases. Recently we identified mutations in FAM83H that caused autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI). Unlike other genes that cause AI, FAM83H does not encode an extracellular matrix protein. Its location inside the cell is completely unknown, as is its function. We here report novel FAM83H mutations in four kindreds with ADHCAI. All are nonsense mutations in the last exon (c.1243G>T, p.E415X; c.891T>A, p.Y297X; c.1380G>A, p.W460X; and c.2029C>T, p.Q677X). These mutations delete between 503 and 883 amino acids from the C-terminus of a protein normally comprised of 1179 residues. The reason these mutations cause such extreme defects in the enamel layer without affecting other parts of the body is not known yet. However it seems evident that the large C-terminal part of the protein is essential for proper enamel calcification.