Beyond the diagnosis: Unraveling DSPP genotype-phenotype correlations in dentin dysplasia and dentinogenesis imperfecta

Abstract

The DSPP gene regulates dentin mineralisation, and its pathogenic variants cause a spectrum of defects ranging from dentin dysplasia (DD-II) to dentinogenesis imperfecta (DGI-II/III). Clinical variability often confounds diagnosis. This systematic review of 48 publications (70 variants, 99 records) delineates quantitative genotype–phenotype correlations. Results revealed distinct molecular clustering: Exon 5 harboured 61 % of variants, predominantly frameshifts disrupting the repetitive dentin phosphoprotein (DPP) domain. In contrast, upstream regions (exons 2–4) contained mixed variant types affecting the signal peptide and dentin sialoprotein (DSP). Statistical analysis established a definitive severity gradient. Exon 5 frameshifts were significantly associated with the milder DD-II, characterised by thistle-shaped pulps and clinically normal permanent dentition. Conversely, upstream signal peptide, splice site, and missense variants (exons 2–3) were linked to the severe DGI-III, manifesting as ‘shell teeth’, rapid attrition, and pulp exposure requiring complex prosthodontic intervention. DGI-II displayed no specific genomic clustering, representing an intermediate phenotype. These findings provide complementary insights to historical classifications, highlighting a continuous spectrum of DSPP disorders where upstream defects cause severe failure, while downstream defects result in attenuated localised anomalies. Consequently, integrating DSPP genotyping into diagnostic workflows is essential to predict disease progression, refine molecular taxonomy beyond the Shields system, and guide personalised rehabilitation.