家族性非综合征型先天缺牙全基因组测序及分析OA
Whole genome sequencing and analysis of familial nonsyndromic congenital tooth agenesis
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.
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 micror-chidia family CW-type zinc finger 4(MORC4)(c.1726C>T,p.Arg576Ter).Among these variants,LAMA2 was associ-ated with a severe tooth agenesis phenotype.The findings offer novel clues toward understanding the etiopathogenesis of this condition.
郑月梅;王丹;蒋彤阳;杨丹曲;卢虹
贵州医科大学口腔医学院,贵阳 550004贵州医科大学口腔医学院,贵阳 550004贵州医科大学口腔医学院,贵阳 550004贵州医科大学口腔医学院,贵阳 550004贵州医科大学附属口腔医院儿童口腔科,贵阳 550004
生物科学
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
nonsyndromic congenital tooth agenesiswhole genome sequencinggene mutationlaminin sub-unit alpha 2
《华西口腔医学杂志》 2026 (2)
206-214,9
Science and Technology Foundation of Guizhou Provincial Health Commission(gzwkj2022-433)Hori-zontal Research Project of Stomatological Hospital of Guizhou Medical University(GYKQ2022HX02) 贵州省卫生健康委科学技术基金(gzwkj2022-433)贵州医科大学附属口腔医院横向课题(GYKQ2022HX02)
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