口腔疾病防治2025，Vol.33Issue(5)：359-367,9.DOI:10.12016/j.issn.2096-1456.202440524
2个非综合征型先天缺牙家系的MSX1基因突变检测与分析
Detection and analysis of MSX1 gene mutations in two families with non-syndromic tooth agenesis
摘要
Abstract
Objective To screen and analyze mutations in two families with non-syndromic tooth agenesis,provid-ing a theoretical basis for the diagnosis and treatment of tooth agenesis.Methods This study was reviewed and ap-proved by the Medical Ethics Committee,and informed consent was obtained from patients.Information and blood sam-ples from two core families with non-syndromic congenital tooth agenesis were collected,along with blood samples from 100 normal controls.Pathogenic gene mutations were explored through whole exome sequencing and Sanger sequencing.The pathogenicity of the identified mutations was analyzed using prediction software Polyphen-2,CADD,and FAMMTH.The impact of the mutations on protein stability was predicted using Mupro,DUET,and I-Mutant software.Conservation analysis and protein 2D/3D structure analysis were used to predict the impact of mutations on protein function.The im-pact of the mutant proteins on subcellular localization was predicted using DeepLoc 2.1 software.Results We identi-fied two novel mutations in the muscle segment homeobox 1(MSX1)gene:c.547C>A(p.Gln183Lys)and c.854T>C(p.Val285Ala)in the two families.Polyphen-2,CADD,and FATHMM predicted these mutations to be pathogenic,and ACMG classified these mutations as likely pathogenic.Conservation analysis showed that the two mutation sites(Gln183 and Val285)are located in highly conserved regions during evolution.Protein stability predictions indicated that these mutations influence protein stability.Protein 2D structure analysis indicated that these two mutations affect the 2D structure of the protein.3D structure analysis showed that these two mutations can cause changes in the 3D structure.Software predictions indicated that these mutations do not affect the subcellular localization of the protein.Conclusion This study is the first to report two novel mutations in the MSX1 gene(c.547C>A and c.854T>C)associated with tooth agenesis,providing a basis for clinical diagnosis and treatment of congenital tooth loss.关键词
先天缺牙/基因突变/肌节同源异性盒基因1/遗传病/发育异常/突变筛查/外显子测序/遗传咨询Key words
tooth agenesis/gene mutation/muscle segment homeobox 1/genetic disorder/developmental anoma-ly/mutation screening/exome sequencing/genetic counseling分类
口腔医学引用本文复制引用
丁婷婷,刘浩辰..2个非综合征型先天缺牙家系的MSX1基因突变检测与分析[J].口腔疾病防治,2025,33(5):359-367,9.基金项目
国家自然科学基金项目(81600851) This study was supported by the grants from the National Natural Science Foundation of China(No.81600851). （81600851）
