Clinical and genetic analysis of a Chinese pedigree affected with Hereditary dentin dysplasia type II due to a variant of DSPP gene.
10.3760/cma.j.cn511374-20241219-00668
- Author:
Fang LI
1
;
Yingting YANG
;
Yang LIU
;
Weifeng TANG
;
Hailan FENG
;
Dong HAN
Author Information
1. 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 for Oral Biomaterials and Digital Medical Devices, Beijing 100081, China. donghan@bjmu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Humans;
Pedigree;
Female;
Extracellular Matrix Proteins/chemistry*;
Male;
Sialoglycoproteins/chemistry*;
Dentin Dysplasia/genetics*;
Asian People/genetics*;
Phosphoproteins/chemistry*;
Child;
Mutation;
China;
Exome Sequencing;
Adult;
East Asian People
- From:
Chinese Journal of Medical Genetics
2025;42(11):1329-1336
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the clinical characteristics and genetic etiology of a Chinese pedigree affected with Hereditary dentin dysplasia type II (DD-II) due to variant of dentin sialophosphoprotein (DSPP) gene.
METHODS:A child diagnosed with DD- II at the Third Clinical Division of Peking University Hospital of Stomatology in December 2021 and her family members were selected as study subjects. Clinical data were retrospectively analyzed. Saliva samples were collected from the proband, her parents and sister for genomic DNA extraction. Whole exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing and TOPO-TA cloning sequencing. The candidate variant was also subjected to bioinformatics analysis using Mutation Taster v2021. Secondary and tertiary structures of the wild-type and variant DSPP proteins were predicted with psipred v4.0 and PyMOL v2.3 software, respectively. The pathogenicity of the variant was classified based on the guidelines from American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Peking University Hospital of Stomatology (Ethics No.: PKUSSIRB-202162021).
RESULTS:The proband and her mother and sister had all exhibited typical clinical manifestations of hereditary DD-II. The primary dentition of the proband displayed yellowish brown discoloration, wear, and obliteration in the chamber and root canal, while the permanent teeth of the proband's sister and mother appeared nearly normal in both color and appearance, though with obliteration in the chamber and root canal. Her father showed normal dentition. WES identified a heterozygous c.1915_1918delAAGT, p.(Lys639Glnfs*674) frameshift variant in the DSPP gene. Sanger sequencing and TOPO-TA cloning sequencing confirmed the presence of this variant in the proband, the proband's sister, and the mother, while the proband's father was negative for the variant, indicating an autosomal dominant inheritance pattern. The variant was predicted to be pathogenic by Mutation Taster v2021. Prediction of the secondary structure of the DSPP protein showed that the variant has changed it from coil to helix. The tertiary structure prediction of the DSPP protein showed change of the spatial structure of the variant DSPP, with the loops in the variant region replaced by helices at multiple sites. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+PM2_Supporting+PP1+PP4).
CONCLUSION:Phenotypic analysis and genetic testing of this family has clarified the clinical diagnosis of hereditary DD- II. The c.1915_1918delAAGT variant probably underlay the pathogenesis of DD-II in this family. Above results have expanded the phenotypic spectrum of the disease and may contribute to further clinical and genetic research on this disease.
