Novel dentin sialophosphoprotein gene frameshift mutations affect dentin mineralization

Zhenwei Zhang; Guibin Huang; Yu Huang; Siyi Liu; Feng Chen; Xuejun Gao; Yanmei Dong; Hua Tian

doi:10.1016/j.archoralbio.2023.105701

Novel dentin sialophosphoprotein gene frameshift mutations affect dentin mineralization

Arch Oral Biol. 2023 Jul:151:105701. doi: 10.1016/j.archoralbio.2023.105701. Epub 2023 Apr 18.

Authors

Zhenwei Zhang¹, Guibin Huang¹, Yu Huang², Siyi Liu¹, Feng Chen³, Xuejun Gao¹, Yanmei Dong⁴, Hua Tian⁵

Affiliations

¹ Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, PR China.
² Department of Medical Genetics, School of Basic Medical Sciences, Peking University Health and Science Center, Beijing, PR China.
³ Central Laboratory, Peking University School and Hospital of Stomatology, National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, PR China.
⁴ Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, PR China. Electronic address: kqdongyanmei@bjmu.edu.cn.
⁵ Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, PR China. Electronic address: hua_tian@bjmu.edu.cn.

PMID: 37084484
DOI: 10.1016/j.archoralbio.2023.105701

Abstract

Objective: This study aimed to identify candidate genes for inheritable dentin defects in three Chinese pedigrees and characterize the property of affected teeth.

Design: Clinical and radiological features were recorded for the affected individuals. Genomic DNA obtained from peripheral venous blood or saliva were analyzed by whole-exome sequencing. The density and microhardness of affected dentin was measured. Scanning electron microscopy (SEM) was also performed to obtain the microstructure phenotype.

Results: 1) General appearance: the affected dentitions shared yellowish-brown or milky color. Radiographs showed that the pulp cavity and root canals were obliterated in varying degrees or exhibited a pulp aspect in the 'thistle tube'. Some patients exhibited periapical infections without pulpal exposure, and some affected individuals showed shortened, abnormally thin roots accompanied by severe alveolar bone loss. 2) Genomic analysis: three new frameshift mutations (NM_014208.3: c.2833delA, c.2852delGand c.3239delA) were identified in exon 5 of dentin sialophosphoprotein (DSPP) gene, altering dentin phosphoprotein (DPP) as result. In vitro studies showed that the density and microhardness of affected dentin were decreased, the dentinal tubules were sparse and arranged disorderly, and the dentinal-enamel-junction (DEJ) was abnormal.

Conclusions: In this study, we identified three novel frameshift mutations of dentin sialophosphoprotein gene related to inherited dentin defects. These mutations are speculated to cause abnormal coding of dentin phosphoprotein C-terminus, which affect dentin mineralization. These results expand the spectrum of dentin sialophosphoprotein gene mutations causing inheritable dentin defects and broaden our understanding of the biological mechanisms by which dentin forms.

Keywords: Dentin phosphoprotein; Dentin sialophosphoprotein; Frameshift mutation; Inheritable dentin defect; Mineralization.

MeSH terms

Dentin
Dentinogenesis Imperfecta* / genetics
Extracellular Matrix Proteins / genetics
Frameshift Mutation*
Humans
Phosphoproteins / genetics
Sialoglycoproteins / genetics

Substances

dentin sialophosphoprotein
Phosphoproteins
Extracellular Matrix Proteins
Sialoglycoproteins