A novel DSPPmutation causes dentinogenesis imperfecta type II in a large Mongolian family

Abstract

BackgroundSeveral studies have shown that the clinical phenotypes of dentinogenesis imperfecta type II (DGI-II) may be caused by mutations in dentin sialophosphoprotein (DSPP). However, no previous studies have documented the clinical phenotype and genetic basis of DGI-II in a Mongolian family from China.MethodsWe identified a large five-generation Mongolian family from China with DGI-II, comprising 64 living family members of whom 22 were affected. Linkage analysis of five polymorphic markers flanking DSPP gene was used to genotype the families and to construct the haplotypes of these families. All five DSPP exons including the intron-exon boundaries were PCR-amplified and sequenced in 48 members of this large family.ResultsAll affected individuals showed discoloration and severe attrition of their teeth, with obliterated pulp chambers and without progressive high frequency hearing loss or skeletal abnormalities. No recombination was found at five polymorphic markers flanking DSPP in the family. Direct DNA sequencing identified a novel A→G transition mutation adjacent to the donor splicing site within intron 3 in all affected individuals but not in the unaffected family members and 50 unrelated Mongolian individuals.ConclusionThis study identified a novel mutation (IVS3+3A→G) in DSPP, which caused DGI-II in a large Mongolian family. This expands the spectrum of mutations leading to DGI-II.

Isolated dentinogenesis imperfecta and dentin dysplasia: revision of the classification

“…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. No mutation has been described within the DGP coding region.…”

miRNA expression profiling identifies DSPP regulators in cultured dental pulp cells

“…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).…”

Hereditary dentine diseases resulting from mutations in DSPP gene

“…Both those and others mutations 44,46-48 that resulted in the skipping of the exon 3 manifested the severe phenotype of dentinogenesis imperfecta type II with progressive attrition and discolouration of teeth and obliteration of pulp chambers; however, there were no accompanying reports of progressive hearing loss. 26,39,46 It is difficult to speculate whether the mutations (but not nonsense mutation) that occur in the DSP sequence of the DSPP gene result exclusively in the disruption of DSP formation or if they influence the DPP protein as well.…”