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

The <i>DSPP</i> 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 <i>DSPP</i> disorders where upstream defects cause severe failure, while downstream defects result in attenuated localised anomalies. Consequently, integrating <i>DSPP</i> genotyping into diagnostic workflows is essential to predict disease progression, refine molecular taxonomy beyond the Shields system, and guide personalised rehabilitation.