Mutation of the signal peptide region of the bicistronic gene DSPP affects translocation to the endoplasmic reticulum and results in defective dentine biomineralization

Rajpar, M. Helen; Koch, Martin Jean; Davies, Robin; Mellody, Kieran T.; Kielty, Cay M.; Dixon, Michael J.

doi:10.1093/hmg/11.21.2559

Cited by 152 publications

(116 citation statements)

References 23 publications

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“…So far, it has been reported that the p.Y6D mutation in the signal peptide prevents the translocation of the mutated N-terminal DSP fragment into the ER in vitro. (20) Mutations in exons 2 and 3 were preliminarily reported to cause retention of the protein to the ER, (21) in line with the presumed impairment of signal peptide cleavage. However, whether any of these mutations have wider effects on ER function or protein export has not been clarified.…”

Section: Discussionmentioning

confidence: 98%

Frameshift mutations in dentin phosphoprotein and dependence of dentin disease phenotype on mutation location

Nieminen

Papagiannoulis-Lascarides

Waltimo‐Sirén

et al. 2010

Journal of Bone and Mineral Research

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We describe results from a mutational analysis of the region of the dentin sialophosphoprotein (DSPP) gene encoding dentin phosphoprotein (DPP) in 12 families with dominantly inherited dentin diseases. In eight families (five mutations in the N-terminal third of DPP), the clinical and radiologic features were uniform and compatible with dentin dysplasia type II (DD-II) with major clinical signs in the deciduous dentition. In the other families (four mutations in the more C-terminal part), the permanent teeth also were affected, and the diseases could be classified as variants of dentinogenesis imperfecta. Attrition was not prominent, but periapical infections were common. Discoloring with varying intensity was evident, and pulps and root canals were obliterated in the permanent dentition. All mutations caused a frameshift that replaced the Ser-Ser-Asx repeat by a code for a hydrophobic downstream sequence of approximately original length. We conclude that frameshift mutations in DSPP explain a significant part of dentin diseases. Furthermore, we propose that the location of the mutation is reflected in the phenotypic features as a gradient from DD-II to more severe disease that does not conform to the classic definitions of DI-II. ß

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Section: Discussionmentioning

confidence: 98%

Frameshift mutations in dentin phosphoprotein and dependence of dentin disease phenotype on mutation location

Nieminen

Papagiannoulis-Lascarides

Waltimo‐Sirén

et al. 2010

Journal of Bone and Mineral Research

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“…56 Description of DSPP mutation in a patient affected by DD-II confirmed this hypothesis and explained these clinical similarities. 57 Towards a nosology defined by mutations spectrum To date 38 pathological variants have been described in the DSPP gene, located in the peptide signal region, within the DSP region and within the DPP region (Table 2). 1,7,28,43,[57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75] Most of them (28) leads to DGI-II, eight to DD-II and two to DGI-III.…”

Section: Dentin Dysplasia Type I or Radicularmentioning

confidence: 99%

Isolated dentinogenesis imperfecta and dentin dysplasia: revision of the classification

Molla¹,

Fournier²,

Berdal³

2014

Eur J Hum Genet

124

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Dentinogenesis imperfecta is an autosomal dominant disease characterized by severe hypomineralization of dentin and altered dentin structure. Dentin extra cellular matrix is composed of 90% of collagen type I and 10% of non-collagenous proteins among which dentin sialoprotein (DSP), dentin glycoprotein (DGP) and dentin phosphoprotein (DPP) are crucial in dentinogenesis. These proteins are encoded by a single gene: dentin sialophosphoprotein (DSPP) and undergo several posttranslational modifications such as glycosylation and phosphorylation to contribute and to control mineralization. Human mutations of this DSPP gene are responsible for three isolated dentinal diseases classified by Shield in 1973: type II and III dentinogenesis imperfecta and type II dentin dysplasia. Shield classification was based on clinical phenotypes observed in patient. Genetics results show now that these three diseases are a severity variation of the same pathology. So this review aims to revise and to propose a new classification of the isolated forms of DI to simplify diagnosis for practitioners.

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“…Extensive evidence indicates that DSPP plays a crucial role during both enamel and dentin biomineralization and/or the formation of the structural diversity of tooth layers (i.e., enamel, mantle dentin, predentin and orthodentin) (1,9,10). DSPP mutations are reported to be associated with DD-II, DGI-II (11)(12)(13)(14)(15)(16)(17)(18)(19)(20) and DGI-III (21), resulting in abnormal dentin formation. Furthermore, DSPP knockout mice display a widened predentin zone and develop defective mineralization similar to human dentinogenesis imperfecta III (22).…”

Section: Introductionmentioning

confidence: 99%

miRNA expression profiling identifies DSPP regulators in cultured dental pulp cells

Huang

Xu²,

Gao³

et al. 2011

Int J Mol Med

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Abstract. Dentin sialophosphoprotein (DSPP), an important marker of odontoblast differentiation, is a prerequisite for tooth development and mineralization; however, the molecular mechanisms of both temporal and spatial regulation remain unknown. MicroRNAs (miRNAs) provide an additional level of control beyond that of transcription factors, which regulate post-transcriptional control of gene expression. The present study was designed to provide a first attempt at an in-depth analysis of dental pulp cells at various odontoblastic differentiation stages to obtain miRNA differential expression patterns, and to determine the contribution of miRNAs in the expression of DSPP during odontoblast differentiation. Dual luciferase reporter assays and qRT-PCR were used to validate miRNAs identified from bioinformatic analyses to determine whether they were able to regulate the DSPP gene in dental pulp cells cultured in a mineralizing medium. The results presented here suggest that DSPP is regulated post-transcriptionally by mir32, mir885-5p and mir586 during odontoblast differentiation.

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Mutation of the signal peptide region of the bicistronic gene DSPP affects translocation to the endoplasmic reticulum and results in defective dentine biomineralization

Cited by 152 publications

References 23 publications

Frameshift mutations in dentin phosphoprotein and dependence of dentin disease phenotype on mutation location

Frameshift mutations in dentin phosphoprotein and dependence of dentin disease phenotype on mutation location

Isolated dentinogenesis imperfecta and dentin dysplasia: revision of the classification

miRNA expression profiling identifies DSPP regulators in cultured dental pulp cells

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