摘要
目的检测1例下切牙先天缺失家系的基因突变情况,确定突变位点并探究突变对蛋白结构和功能的潜在影响,为下切牙先天缺失的发生机制提供新的见解。方法通过全外显子组测序及Sanger测序筛选该家系可能的致病基因,并对验证后的基因进行功能预测及突变位点氨基酸保守性分析。利用AlphaFold和PyMOL预测该蛋白的三维结构。使用小鼠基因组信息学和时空转录组图谱对候选基因表达进行分析。使用单细胞RNA测序数据分析白细胞受体簇成员9(leukocyte receptor cluster member 9,LENG9)基因可能参与调控的下游通路。结果在临床诊疗过程中发现1例下切牙先天缺失的家系。先证者及先证者的弟弟存在先天缺失下切牙的表型,先证者两侧磨牙远中关系、尖牙远中关系、上前牙轻度拥挤、下颌散在间隙、深覆牙合、深覆盖,而先证者的父母无缺牙表型。通过全外显子组测序发现在LENG9基因外显子1上存在(c.392C>T:p.Arg131His)的突变,且第131号的精氨酸在各物种间具有高度保守性。生物信息学分析显示LENG9在颌骨和牙齿中有表达。GO和KEGG通路注释分析表明,LENG9可能通过调控氧化磷酸化相关通路参与先天缺牙的发生。结论本研究报道了1例下切牙先天缺失的家系和1个LENG9(c.392C>T:p.Arg131His)的新发突变,研究结果提示该突变可能是导致该家系下切牙先天缺失的致病基因。
Objective To investigate mutations in a family lineage with congenital absence of lower incisors,identify mutation sites and explore the effects of mutations on protein structure and function to provide new insights into the mechanisms underlying the development of congenital absence of lower incisors.Methods Whole-exome sequencing and Sanger sequencing were used to screen the possible causative genes in this family lineage.The validated genes were analyzed for functional prediction and amino acid conservation at the mutation sites.The three-dimensional structure of the protein was predicted by AlphaFold and PyMOL.Candidate gene expression was analyzed using mouse genome informatics and the spatiotemporal transcriptome atlas.Single-cell RNA sequencing data were used to analyze downstream pathways potentially regulated by the LENG9 gene.Results A family pedigree with congenital absence of lower incisors was identified during clinical practice.A phenotype of congenitally missing lower incisors was present in the proband and the proband s younger brother.The proband had distal molar relationship and distal canine relationship on both sides,mild crowding of upper anterior teeth,scattered spaces in the mandible,and deep overbite as well as deep overjet,whereas the proband s parents did not have a missing tooth phenotype.Through whole-exome sequencing,a mutation(c.392C>T:p.Arg131His)was identified in exon 1 of the LENG9 gene,and the arginine at position 131 was highly conserved among various species.Bioinformatics analyses showed that LENG9 was expressed in the jaws and teeth.GO and KEGG pathway annotation analyses indicated that LENG9 may play a role in the pathogenesis of congenital tooth agenesis by regulating oxidative phosphorylation-related pathways.Conclusion In this study,we report a family lineage with congenital absence of lower incisors and a de novo mutation in LENG9(c.392C>T:p.Arg131His),and the findings suggest that the mutation LENG9 may be the causative gene responsible for the congenital absence of lower incisors in this family lineage with congenital tooth agenesis.
作者
冒纪
张欣瑜
程婷婷
马兰
潘永初
MAO Ji;ZHANG Xinyu;CHENG Tingting;MA Lan;PAN Yongchu(Department of Orthodontics,The Affiliated Stomatological Hospital of Nanjing Medical University,Nanjing 210029,China)
出处
《口腔医学》
2026年第3期161-166,共6页
Stomatology
基金
江苏省科教能力提升工程——江苏省研究型医院(YJXYYJSDW4)
江苏省医学创新中心(CXZX202227)。
