Whole genome sequencing and analysis of familial nonsyndromic congenital tooth agenesis

doi:10.7518/hxkq.2026.2025131

Abstract

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

CLC Number:

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