家族性非综合征型先天缺牙全基因组测序及分析

doi:10.7518/hxkq.2026.2025131

摘要/Abstract

摘要：

先天缺牙不仅损害患者咀嚼功能及美观，还会影响颌面部发育。该疾病主要由遗传导致，但确切病因目前尚不明确。本文报道的3例非综合征型先天缺牙（NSTA）患者为同一家庭成员，全基因组测序（WGS）筛选出5个致病性变异基因：细丝蛋白B（FLNB）（c.5186C>A，p.Ser1729Ter）、甲基巴豆酰辅酶a羧化酶2（MCCC2）（c.91C>T，p.Gln31Ter；c.484C>T，p.Gln162Ter；c.340C>T，p.Gln114Ter）、层粘连蛋白亚基α2（LAMA2）（c.1084A>T，p.Arg362Ter）、组织蛋白酶C（CTSC）（c.748C>T，p.Arg250Ter）、染色质重塑蛋白家族CW型锌指结构蛋白4（MORC4）（c.1726C>T，p.Arg576Ter），其中LAMA2变异与更严重的先天缺牙表型存在相关性，这为理解该疾病的病因机制提供了新线索。

关键词: 非综合征型先天缺牙, 全基因组测序, 基因突变, 层粘连蛋白亚基α2

Abstract:

Congenital tooth agenesis impairs masticatory function and aesthetics and adversely affects craniofacial development. Although largely considered genetic in origin, its exact etiology remains unclear. This study reports three familial cases of nonsyndromic congenital tooth agenesis (NSTA). Whole genome sequencing (WGS) revealed five pathogenic variants: filamins-B (FLNB) (c.5186C>A, p.Ser1729Ter), methylcrotonyl coenzyme a carboxylase 2 (MCCC2) (c.91C>T, p.Gln31Ter; c.484C>T, p.Gln162Ter; c.340C>T, p.Gln114Ter), laminin subunit alpha 2 (LAMA2) (c.1084A>T, p.Arg362Ter), cathepsin C (CTSC) (c.748C>T, p.Arg250Ter), and chromatin remodeling protein microrchidia family CW-type zinc finger 4 (MORC4) (c.1726C>T, p.Arg576Ter). Among these variants, LAMA2 was associated with a severe tooth agenesis phenotype. The findings offer novel clues toward understanding the etiopathogenesis of this condition.

Key words: nonsyndromic congenital tooth agenesis, whole genome sequencing, gene mutation, laminin subunit alpha 2

中图分类号:

郑月梅, 王丹, 蒋彤阳, 杨丹曲, 卢虹. 家族性非综合征型先天缺牙全基因组测序及分析[J]. 华西口腔医学杂志, 2026, 44(2): 206-214.

Zheng Yuemei, Wang Dan, Jiang Tongyang, Yang Danqu, Lu Hong. Whole genome sequencing and analysis of familial nonsyndromic congenital tooth agenesis[J]. West China Journal of Stomatology, 2026, 44(2): 206-214.

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序号	临床表征	Ⅲ1	Ⅲ2	Ⅲ3
1	特征性面容（前额突出、眶周皮肤色素沉着、眼距过宽、耳廓突出、口唇肥厚、鼻梁扁平或鞍状鼻、其他特征性面容）	否	否	否
2	毛发稀疏	否	否	否
3	皮肤干燥而多皱纹	否	否	否
4	不出汗或很少出汗	否	否	否
5	不能耐高温	否	否	否
6	指（趾）发育不良	否	否	否
7	躯体发育迟缓（矮小）	否	否	否
8	智力发育迟缓	否	否	否
9	是否伴有唇腭裂	否	否	否
10	视力异常	否	否	否
11	心脏功能异常	否	否	否
12	免疫功能异常	否	否	否
13	全身其他状况（包括肾脏疾病、血液系统疾病、消化系统疾病、心血管疾病、糖尿病等）	否	否	否

序号	基因	转录本ID	外显子	cDNA变异	蛋白质变异	ACMG分类证据
1	FLNB（Ⅲ1、Ⅲ2、Ⅲ3杂合突变）	ENST00000493452.5	33	c.5186C>A	p.Ser1729Ter	PVS1+PM2+PP3
2	MCCC2（Ⅲ1、Ⅲ2、Ⅲ3杂合突变）	ENST00000682214.1	4	c.91C>T	p.Gln31Ter	PVS1+PM2+PP3
		ENST00000340941.11	5	c.484C>T	p.Gln162Ter	PVS1+PM2+PP3
		ENST00000682045.1	5	c.340C>T	p.Gln114Ter	PVS1+PM2+PP3
3	LAMA2（Ⅲ1杂合突变）	ENST00000421865.3	8	c.1084A>T	p.Arg362Ter	PVS1+PM2+PP3
4	CTSC（Ⅲ1、Ⅲ2、Ⅲ3杂合突变）	ENST00000227266.10	5	c.748C>T	p.Arg250Ter	PVS1+PM2+PP3
5	MORC4（Ⅲ2杂合突变）	ENST00000255495.7	15	c.1726C>T	p.Arg576Ter	PVS1+PM2+PP3