We identified two homozygous missense variants (c.428C>T, p.(T143M) and c.746C>T, p.(P249L)) in ACPT, the gene encoding acid phosphatase, testicular, which segregates with hypoplastic amelogenesis imperfecta in two unrelated families. ACPT is reported to play a role in odontoblast differentiation and mineralisation by supplying phosphate during dentine formation. Analysis by computerised tomography and scanning electron microscopy of a primary molar tooth from an individual homozygous for the c.746C>T variant revealed an enamel layer that was hypoplastic, but mineralised with prismatic architecture. These findings implicate variants in ACPT as a cause of early failure of amelogenesis during the secretory phase.

Amelogenesis is the process of enamel formation. For amelogenesis to proceed, the cells of the inner enamel epithelium (IEE) must first proliferate and then differentiate into the enamel-producing ameloblasts. Amelogenesis imperfecta (AI) is a heterogeneous group of genetic conditions that result in defective or absent tooth enamel. We identified a 2 bp variant c.817_818GC>AA in SP6, the gene encoding the SP6 transcription factor, in a Caucasian family with autosomal dominant hypoplastic AI. The resulting missense protein change, p.(Ala273Lys), is predicted to alter a DNA-binding residue in the first of three zinc fingers. SP6 has been shown to be crucial to both proliferation of the IEE and to its differentiation into ameloblasts. SP6 has also been implicated as an AI candidate gene through its study in rodent models. We investigated the effect of the missense variant in SP6 (p.(Ala273Lys)) using surface plasmon resonance protein-DNA binding studies. We identified a potential SP6 binding motif in the AMBN proximal promoter sequence and showed that wild-type (WT) SP6 binds more strongly to it than the mutant protein. We hypothesize that SP6 variants may be a very rare cause of AI due to the critical roles of SP6 in development and that the relatively mild effect of the missense variant identified in this study is sufficient to affect amelogenesis causing AI, but not so severe as to be incompatible with life. We suggest that current AI cohorts, both with autosomal recessive and dominant disease, be screened for SP6 variants.

Intraosseous xanthomas are rare, benign entities and may present a diagnostic challenge to clinicians, radiologists and histopathologists due to the non‐specific features of this lesion. Presented here is the first definitive reported recurrence of an intraosseous xanthoma, which was previously diagnosed as a granular cell odontogenic tumour. We include a review of the existing literature and discuss the diagnostic pitfalls in navigating the differences between granular cell odontogenic tumour and intraosseous xanthoma.

Since the discovery of bioactive molecules sequestered in dentine, researchers have been exploring ways to harness their activities for dental regeneration. One specific area, discussed in this review, is that of dental-pulp capping. Dental-pulp caps are placed when the dental pulp is exposed due to decay or trauma in an attempt to enhance tertiary dentine deposition. Several materials are used for dental-pulp capping; however, natural biomimetic scaffolds may offer advantages over manufactured materials such as improved aesthetic, biocompatibility and success rate. The present review discusses and appraises the current evidence surrounding biomimetic dental-pulp capping, with a focus on bioactive molecules sequestered in dentine. Molecules covered most extensively in the literature include transforming growth factors (TGF-βs, specifically TGF-β1) and bone morphogenetic proteins (BMPs, specifically BMP-2 and BMP-7). Further studies would need to explore the synergistic use of multiple peptides together with the development of a tailored scaffold carrier. The roles of some of the molecules identified in dentine need to be explored before they can be considered as potential bioactive molecules in a biomimetic scaffold for dental-pulp capping. Future in vivo work needs to consider the inflammatory environment of the dental pulp in pulpal exposures and compare pulp-capping materials.