常染色体显性钙化不全型釉质发育不全相关基因序列相似性83蛋白质家族成员H及其突变的研究进展

doi:10.7518/gjkq.2022086

摘要/Abstract

摘要：

常染色体显性钙化不全型釉质发育不全（ADHCAI）是一种影响釉质结构的遗传性疾病，基本病变为釉质基质形成正常但无明显的矿化。该疾病具有明显的临床和遗传异质性，临床表现为患牙的釉质厚度正常而硬度降低，影响功能和美观。序列相似性83蛋白质家族成员H （FAM83H）在人体的多种组织和细胞中普遍表达，包括成釉细胞、成牙本质细胞和牙槽骨。该基因编码的细胞内蛋白质被认为与角蛋白细胞骨架和桥粒相关，在细胞内分子运输、细胞骨架网络调节和釉质形成中发挥作用。FAM83H基因中的许多突变已被证实可在不同人群中导致ADHCAI。近年来一些研究从囊泡运输、细胞骨架等多角度入手，探究FAM83H突变与ADHCAI发生发展之间的关系，本文就ADHCAI相关基因FAM83H及其突变的研究进展进行综述。

关键词: 常染色体显性钙化不全型釉质发育不全, 序列相似性83蛋白质家族成员H, 截断突变

Abstract:

Autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI) is a genetic disorder characterized by abnormal enamel formation. The enamel matrix is formed normally but without apparent mineralization. The ADHCAI has evident clinical and genetic heterogeneity. The affected tooth’s enamel thickness is normal however, the surface hardness is reduced, thus affecting the tooth’s function and aesthetics. Family with sequence similarity 83 member H (FAM83H) is a member of family with sequence similarity 83. It is widely expressed in a variety of human tissues and cells including ameloblasts, odontoblasts, and alveolar bone. It encodes an intracellular protein that is associated with keratin cytoskeleton and desmosomes, playing a role in intracellular molecular transport, cytoskeletal network regulation, and enamel formation. Various mutations have been identified in the FAM83H gene that leads to ADHCAI in different populations. In recent years, several studies explored the relationship between mutations in FAM83H and the occurrence and development of ADHCAI from multiple perspectives, such as vesicle trafficking and cytoskeletal organization. In this review, we will focus on the research progress on the gene FAM83H related to ADHCAI and its mutation.

Key words: autosomal dominant hypocalcified amelogenesis imperfecta, family with sequence similarity 83 member H, truncation mutation

中图分类号:

R 780.2

郭思敏,陈婷. 常染色体显性钙化不全型釉质发育不全相关基因序列相似性83蛋白质家族成员H及其突变的研究进展[J]. 国际口腔医学杂志, 2022, 49(5): 600-606.

Guo Simin,Chen Ting. Research progress on the gene family with sequence similarity 83 member H related to autosomal dominant hypocalcified amelogenesis imperfecta and its mutation[J]. Int J Stomatol, 2022, 49(5): 600-606.

图/表 1

表 1

已报道的与ADHCAI有关的FAM83突变"

编号	cDNA	蛋白质	家系	口腔临床表现						全景片表现	首次发表的作者及年份
编号	cDNA	蛋白质	家系	萌出前釉质厚度	萌出后釉质磨损的程度	萌出后釉质质地	牙齿颜色	有无前牙开??	对热刺激敏感程度	釉质放射密度与牙本质接近	首次发表的作者及年份
1	c.973C>T	p.R325*	韩国	-	++	柔软	*	+	++	*	Kim等^[8]（2008）
2	c.1192C>T	p.Q398*	韩国	-	++	柔软	*	+	++	*	Kim等^[8]（2008）
3	c.1243G>T	p.E415*	西班牙	-	+++	柔软	浅黄色	*	++	*	Lee等^[10]（2008）
4	c.891T>A	p.Y297*	亚洲人	-	+++	柔软	浅黄色	*	++	*
5	c.1380G>A	p.W460*	白种人	-	+++	柔软	浅黄色	*	++	*
6	c.2029C>T	p.Q677*	白种人	-	+++	柔软	浅黄色	*	++	*
7	c.1330C>T	p.Q444*	土耳其	*	*	*	*	*	*	*	Hart 等^[11]（2009）
8	c.1366C>T	p.Q456*	土耳其	*	*	*	*	*	*	*	Hart 等^[11]（2009）
9	c.1354C>T	pQ452*	韩国	-	++	柔软	棕色	*	+	*	Hyun等^[12]（2009）
10	c.1408C>T	p.Q470*	白种人	*	*	*	*	*	*	*	Wright等^[13]（2009）
11	c.860C>A	p.S287*	白种人	*	*	*	*	*	*	*
12	c.1379G>A	p.W460*	白种人	*	*	*	*	*	*	*
13	c.2080G>T	p.E694*	白种人	*	*	*	*	*	*	*
14	c.923_924delTC	p.L308fs*323	白种人	*	*	*	*	*	*	*
15	c.1872_1873delCC	p.L625fs*703	白种人	*	*	*	*	*	*	*
16	c.1374C>A	p.Y458*	欧洲人	*	++	柔软	黄色	*	++	+	EL-Sayed等^[14]（2010）
17	c.906T>A	p.Y302*	丹麦	-	++	柔软	黄棕色	+	*	+	Haubek等^[15]（2011）
18	c.1354C>T	p.Q452*	丹麦	-	++	柔软	黄棕色	+	*	+	Haubek等^[15]（2011）
19	c.906T>G	p.Y302*	中国	*	++	柔软	淡黄色	-	++	*	Song等^[16]（2012）
20	c.924dupT	p.V309Rfs*324	中国	*	++	柔软	黄棕色	-	++	*
21	c.1354C>T	pQ452*	中国	*	++	柔软	黄棕色	-	++	*
22	c.2029 C>T	p.Q677*	中国	*	++	柔软	黄棕色	-	++	*
23	c.1669G>T	p.Gly557Cys	智利	-	+++	柔软	黄棕色	*	++	+	Urzúa等^[9]（2015）
24	c.1387C>T	p.Gln463X;	泰国	-	+++	柔软	黄黑色	+	++	*	Kantaputra等^[17]（2016）
25	c.1369C>T	p.Gln457*	土耳其	-	+++	柔软	黄棕色	*	*	+	Wang等^[3]（2016）
26	c.1915A>T	p.Lys639*	台湾	-	+++	柔软	黄棕色	+	*	+	Wang等^[3]（2016）
27	c.931dupC	p.V311Rfs*13	中国	*	+++	柔软	黄棕色	*	*	*	Wang等^[18]（2017）
28	c.1130_1131delinsAA	p.S377X	中国	-	++	柔软	黄棕色	*	*	+
29	c.1147G > T	p.E383X	中国	*	+++	*	深棕色	+	*	*
30	c.1261G>T	p.E421*	泰国	-	+++	*	黄棕色	*	*	+	Nowwarote等^[5]（2018）
31	c.1222A>T	p.K408X	中国	*	+++	柔软	黑棕色	+	*	+	Yu等^[19]（2018）
32	c.1309_1311delinsTAA	p.His437*	台湾	-	+++	*	深棕色	*	*	+	Wang等^[20]（2021）
33	c.1375C>T	p.Gln459*	白种人	*	+++	*	黄棕色	*	*	+
34	c.1828G>T	p.Glu610*	台湾	*	+++	*	黑棕色	*	*	*

表 1

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