Novel DLX3 variants in amelogenesis imperfecta with attenuated tricho-dento-osseous syndrome.

OBJECTIVES: Variants in DLX3 cause tricho-dento-osseous syndrome (TDO, MIM #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, six different DLX3 variants have been reported in TDO. The aim of this paper was to explore and discuss three recently uncovered new variants in DLX3. SUBJECTS AND 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 two further families revealed another new variant of DLX3 and complete heterozygous deletion of DLX3. For all three families, the phenotypes were shown to consist of AI and taurodontism, together with other attenuated features of TDO. RESULTS: c.574delG p.(E192Rfs*66), c.476G>T (p.R159L) and a heterozygous deletion of the entire DLX3 coding region were identified in our families. CONCLUSION: These previously unreported variants add to the growing literature surrounding AI, allowing for more accurate genetic testing and better understanding of the associated clinical consequences.

PLATOON: Premature Loss of bAby Teeth and its impact On Orthodontic Need - protocol.

OBJECTIVE: To investigate the impact of premature extraction of primary teeth (PEPT) on orthodontic treatment need in a cohort of children participating in the Born in Bradford (BiB) longitudinal birth cohort. DESIGN: Observational, cross-sectional cohort. PARTICIPANTS: We aim to recruit 1000 children aged 7-11 years: 500 with a history of PEPT and 500 matched non-PEPT controls. METHODS: After informed consent/assent, orthodontic records will be collected, including extra and intra-oral photographs and alginate impressions for study models. Participants will also complete a measure of oral health-related quality of life (COHIP-SF 19). The records will be used to quantify space loss, identify other occlusal anomalies and assess orthodontic treatment need using the Index of Orthodontic Treatment Need. For each outcome, summary statistics will be calculated and the data for children with and without PEPT compared. The records of the children identified to be in need of orthodontic treatment will be examined by an expert orthodontic panel to judge if this treatment should be undertaken at the time of the records or delayed until the early permanent dentition. Collecting robust records in the mixed dentition provides the clinical basis to link each stage of the causal chain and enable the impact of PEPT on orthodontic need to be characterised. This study is the first to provide the foundations for future longitudinal data collection allowing the long-term impact of PEPT to be studied.