Detection and analysis of MSX1 gene mutations in two families with non-syndromic tooth agenesis
10.12016/j.issn.2096-1456.202440524
- Author:
DING Tingting
1
;
LIU Haochen
2
Author Information
1. Department of Stomatology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health
2. Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Central Laboratory
- Publication Type:Journal Article
- Keywords:
ooth agenesis;
gene mutation;
muscle segment homeobox 1;
genetic disorder;
developmental anomaly;
mutation screening;
exome sequencing;
genetic counseling
- From:
Journal of Prevention and Treatment for Stomatological Diseases
2025;33(5):359-367
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To screen and analyze mutations in two families with non-syndromic tooth agenesis, providing a theoretical basis for the diagnosis and treatment of tooth agenesis
Methods:This study was reviewed and approved by the Medical Ethics Committee, and informed consent was obtained from patients. Information and blood samples 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 impact of the mutant proteins on subcellular localization was predicted using DeepLoc 2.1 software.
Results:We identified 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.
- Full text:20250507160035970232个非综合征型先天缺牙家系的MSX1基因突变检测与分析.pdf
