Translated Mutant DSPP mRNA Expression Level Impacts the Severity of Dentin Defects

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Kim Y. J., Lee Y., Zhang H., Seymen F., Koruyucu M., Bayrak S., ...More

JOURNAL OF PERSONALIZED MEDICINE, vol.12, no.6, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 12 Issue: 6
  • Publication Date: 2022
  • Doi Number: 10.3390/jpm12061002
  • Journal Name: JOURNAL OF PERSONALIZED MEDICINE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, EMBASE, Directory of Open Access Journals
  • Keywords: hereditary, splicing mutation, dentinogenesis imperfecta, dentin sialophosphoprotein, DSPP, silent mutation, genotype-phenotype relationship, DENTINOGENESIS IMPERFECTA, ENDOPLASMIC-RETICULUM, SIALOPHOSPHOPROTEIN MUTATION, DYSPLASIA, TRAFFICKING, GENOTYPE
  • Istanbul University Affiliated: Yes

Abstract

Hereditary dentin defects are conventionally classified into three types of dentinogenesis imperfecta (DGI) and two types of dentin dysplasia (DD). Mutations in the dentin sialophosphoprotein (DSPP) gene have been identified to cause DGI type II and III and DD type II; therefore, these are not three different conditions, but rather allelic disorders. In this study, we recruited three families with varying clinical phenotypes from DGI-III to DD-II and performed mutational analysis by candidate gene analysis or whole-exome sequencing. Three novel mutations including a silent mutation (NM 014208.3: c.52-2del, c.135+1G>C, and c.135G>A; p.(G1n45=)) were identified, all of which affected pre-mRNA splicing. Comparison of the splicing assay results revealed that the expression level of the DSPP exon 3 deletion transcript correlated with the severity of the dentin defects. This study did not only expand the mutational spectrum of DSPP gene, but also advanced our understanding of the molecular pathogenesis impacting the severity of hereditary dentin defects.