A DSPP mutation causing dentinogenesis imperfecta and characterization of the mutational effect.

Mutations in the DSPP gene have been identified in nonsyndromic hereditary dentin defects, but the genotype-phenotype correlations are not fully understood. Recently, it has been demonstrated that the mutations of DSPP affecting the IPV leader sequence result in mutant DSPP retention in rough endopl...

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Publicado en:BioMed Research International Vol. 2013; pp. 948181 - 948182
Autores principales: Lee, Sook-Kyung, Lee, Kyung-Eun, Song, Su Jeong, Hyun, Hong-Keun, Lee, Sang-Hoon, Kim, Jung-Wook
Formato: research Journal Article
Publicado: Wiley-Blackwell 2013
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 2013
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        atl: A DSPP mutation causing dentinogenesis imperfecta and characterization of the mutational effect.
      aug:
        au:
          Lee, Sook-Kyung
          Lee, Kyung-Eun
          Song, Su Jeong
          Hyun, Hong-Keun
          Lee, Sang-Hoon
          Kim, Jung-Wook
        affil: Department of Pediatric Dentistry and Dental Research Institute, School of Dentistry, Seoul National University, 275-1 Yongon-dong, Chongno-gu, Seoul 110-768, Republic of Korea.
      sug:
        subj:
          Dentinogenesis Imperfecta
          Proteins
          Mutation
          Phosphoproteins
          Glycoproteins
          Adult
          Aged
          Animals
          Primates
          Sequence Analysis
          Dentin Physiology
          Cytoplasm Metabolism
          Female
          Human
          Infant
          Male
          Pedigree
          South Korea
          Adult: 19-44 years
          Aged: 65+ years
          Infant: 1-23 months
          Female
          Male
      ab: Mutations in the DSPP gene have been identified in nonsyndromic hereditary dentin defects, but the genotype-phenotype correlations are not fully understood. Recently, it has been demonstrated that the mutations of DSPP affecting the IPV leader sequence result in mutant DSPP retention in rough endoplasmic reticulum (ER). In this study, we identified a Korean family with dentinogenesis imperfecta type III. To identify the disease causing mutation in this family, we performed mutational analysis based on candidate gene sequencing. Exons and exon-intron boundaries of DSPP gene were sequenced, and the effects of the identified mutation on the pre-mRNA splicing and protein secretion were investigated. Candidate gene sequencing revealed a mutation (c.50C > T, p.P17L) in exon 2 of the DSPP gene. The splicing assay showed that the mutation did not influence premRNA splicing. However, the mutation interfered with protein secretion and resulted in the mutant protein remaining largely in the ER. These results suggest that the mutation affects ER-to-Golgi apparatus export and results in the reduction of secreted DSPP and ER overload. This may induce cell stress and damage processing and/or transport of dentin matrix proteins or other critical proteins.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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