Abstract - Text

Abstract-Text

Heritable dentin defects are rare diseases affecting both deciduous and permanent teeth, which present with abnormally mineralized dentin. Based on clinical manifestations and imaging features, these diseases were classified into dentinogenesis imperfecta and dentin dysplasia (two subtypes: DD-I and DD-II). Dentin dysplasia type I is a hereditary tooth disorder with an incidence rate of 1 per 1x105 in Europe. It is characterized by deformations in dentine structure and mineralization as well as root formation. DD-Ib is associated with shortened roots, severely obliterated pulps with ubiquitary apical osteolysis in both child and adult dentition. Although some preservative strategies have been developed, preterm tooth loss remains inevitable. Despite the fact that DD-I is a special dentin genetic disease, there is no consensus in literature concerning the definition, classification, clinical features, etiology, diagnosis, differential diagnosis, or treatment. Investigators widely speculated about the pathogenesis of DD in earlier studies. Some genes have been described as possible causative candidates for DD: SMOC2, SSUH2 and VPS4B. Here, we identified a new candidate gene for DD-Ib.

In this study we describe four individuals of a three-generation family affected with severe DD and one unaffected individual. All four of them displayed DD-Ib characteristics in panoramic radiography but no abnormality in clinical tooth morphology. Root deformation was accompanied by severe inflammation and osseous defects.

We performed whole exome sequencing (WES) on the five family members (n=5) to identify causative variants for DD and filtered for variants segregating with the disease. All affected individuals but not the unaffected family member carried a heterozygous variant in EVPL (c.807+4_807+5insCGACCT; NM_001329747.2) predicted to lead to loss of the donor splice site of exon 7. EVPL encodes for a protein of the plakin family. The protein is a part of the desmosomes and the epidermal cornified envelope. EVPL has never been described in this special disease context until now. Further studies are ongoing to enroll additional individuals for segregation analysis and to analyze the real effect of the variant on RNA splicing and subsequently, functional analyses are planned to shed more light into the role of EVPL in DD aiming at gaining better treatment options for DD.