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., ...Daha Fazla

JOURNAL OF PERSONALIZED MEDICINE, cilt.12, sa.6, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 12 Sayı: 6
  • Basım Tarihi: 2022
  • Doi Numarası: 10.3390/jpm12061002
  • Dergi Adı: JOURNAL OF PERSONALIZED MEDICINE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, EMBASE, Directory of Open Access Journals
  • Anahtar Kelimeler: hereditary, splicing mutation, dentinogenesis imperfecta, dentin sialophosphoprotein, DSPP, silent mutation, genotype-phenotype relationship, DENTINOGENESIS IMPERFECTA, ENDOPLASMIC-RETICULUM, SIALOPHOSPHOPROTEIN MUTATION, DYSPLASIA, TRAFFICKING, GENOTYPE
  • İstanbul Üniversitesi Adresli: Evet

Özet

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.