Frameshift mutation in RELT gene causes amelogenesis imperfecta
10.19723/j.issn.1671-167X.2025.01.003
- VernacularTitle:RELT基因移码突变导致遗传性釉质发育不全
- Author:
Zhenwei ZHANG
1
;
Xinran XU
;
Xuejun GAO
;
Yanmei DONG
;
Hua TIAN
Author Information
1. 北京大学口腔医学院·口腔医院牙体牙髓科,国家口腔医学中心,国家口腔疾病临床医学研究中心,口腔生物材料和数字诊疗装备国家工程研究中心,北京 100081;复旦大学附属上海市口腔医院牙体牙髓二科,上海市颅颌面发育与疾病重点实验室,上海 200001
- Publication Type:Journal Article
- Keywords:
Amelogenesis imperfecta;
RELT gene;
Frameshift mutation;
Enamel mineralization
- From:
Journal of Peking University(Health Sciences)
2025;57(1):13-18
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze RELT gene mutation found in a pedigree with clinical features and inheritable pattern consistent with amelogenesis imperfecta(AI)in China,and to study the relationship between its genotype and phenotype.Methods:Clinical and radiological features were recorded for the affected individuals.Peripheral venous blood samples of the patient and family members were collected for further study,and the genomic DNA was extracted to identify the pathogenic gene.Whole exome sequencing(WES)was performed to analyze the possible pathogenic genes,and Sanger sequencing was performed for validation.SIFT and PolyPhen-2 were used to predict and analyze the mutation effect.Comparison of RELT amino acids across different species were performed by using Uniprot website.In addition,the three-dimen-sional structures of the wild type and mutant proteins were predicted by Alphafold 2.Results:The proband exhibited typical hypocalcified AI,with heavy wear,soft enamel,rough and discolored surface,and partial enamel loss,while his parents didn't have similar manifesta-tions.WES and Sanger sequencing results indicated that the proband carries a homozygous frameshift mu-tation in RELT gene,NM_032871.3:c.1169_1170del,and both of his parents were carriers.This mu-tation was predicted to be pathogenic by SIFT and Poly Phen-2.Up to now,there were 11 mutation sites in RELT gene were reported to be associated with AI,and all of the patients exhibited with hypocalcified AI.Compared with the wild-type RE LT protein,the mutant protein p.Pro390fs35 conformation terminated prematurely,affecting the normal function of the protein.Conclusion:Through phenotype analysis,gene sequencing,and functional prediction of a Chinese family with typical amelogenesis imperfecta,this study found that RELT gene frameshift mutation can lead to protein dysfunction in AI patients.Further research will focus on the role and mechanism of RELT in enamel development at the molecular and animal levels,providing molecular biology evidence for the genetic counseling,prenatal diagnosis,and early prevention and treatment of AI.
