LAUSR

Background Variants in DLX3 cause tricho-dento-osseous syndrome (TDO; MIM accession no. 190320), a systemic condition with hair, nail, and bony changes, taurodontism, and amelogenesis imperfecta (AI) inherited in an autosomal dominant fashion. Different variants found within this gene are associated with different phenotypic presentations. To date, 6 different DLX3 variants have been reported in TDO. The aim of this paper is to explore and discuss 3 recently uncovered new variants in DLX3 and their resulting phenotypes. Objective To identify new variants associated with AI to increase the accuracy of genetic testing and elucidate the roles and functions of genes involved in amelogenesis. In this study, 3 new variants within DLX3 were identified as being associated with AI. Methods Whole-exome sequencing identified a new DLX3 variant in one family recruited as part of an ongoing study of genetic variants associated with AI. Targeted clinical exome sequencing of 2 further families revealed another new variant of DLX3 and a complete heterozygous deletion of DLX3. For all 3 families, the phenotypes consisted of AI and taurodontism, together with other attenuated features of TDO. Conclusions c.574delG p.(E192Rfs*66), c.476G>T (p.R159L), and a heterozygous deletion of the entire DLX3 coding region were identified in the families studied. These previously unreported variants add to the growing literature surrounding AI, allowing more accurate genetic testing and better understanding of the associated clinical consequences.