Novel mutations in LRP6 highlight the role of WNT signaling in tooth agenesis.

PURPOSE: We aimed to identify a novel genetic cause of tooth agenesis (TA) and/or orofacial clefting (OFC) by combining whole-exome sequencing (WES) and targeted resequencing in a large cohort of TA and OFC patients. METHODS: WES was performed in two unrelated patients: one with severe TA and OFC and another with severe TA only. After deleterious mutations were identified in a gene encoding low-density lipoprotein receptor-related protein 6 (LRP6), all its exons were resequenced with molecular inversion probes in 67 patients with TA, 1,072 patients with OFC, and 706 controls. RESULTS: We identified a frameshift (c.4594delG, p.Cys1532fs) and a canonical splice-site mutation (c.3398-2A>C, p.?) in LRP6, respectively, in the patient with TA and OFC and in the patient with severe TA only. The targeted resequencing showed significant enrichment of unique LRP6 variants in TA patients but not in nonsyndromic OFC patients. Of the five variants in patients with TA, two affected the canonical splice site and three were missense variants; all variants segregated with the dominant phenotype, and in one case the missense mutation occurred de novo. CONCLUSION: Mutations in LRP6 cause TA in humans.Genet Med 18 11, 1158-1162.

Tooth agenesis patterns and phenotype variation in a cohort of Belgian patients with hypodontia and oligodontia clustered in 79 families with their pedigrees.

BACKGROUND: Even though tooth agenesis is the most common developmental anomaly of the human dentition, its genetic background and pathogenic mechanism(s) still remain poorly understood. Syndromic and isolated forms of hypodontia have been described and can occur sporadically or in families. OBJECTIVES: We describe and analyse the hypo-/oligodontia phenotype variations in families. The index patient suffers from severe or mild hypodontia; case-parents/sib records are available. Furthermore, we aim to evaluate whether the different agenesis patterns in the pedigrees are predictive of mutations in specific genes based on reported genotype-phenotype associations. MATERIALS AND METHODS: Dental records and pedigrees were collected from 79 families. In 67 families, the index patient presented with oligodontia while in 12 families with hypodontia. The phenotype data of 66 oligodontia index patients were analysed with the Tooth Agenesis Code software. RESULTS: Nine families counted two members; one family counted three members affected with oligodontia. Twenty-four oligodontia families respectively had one (n = 17), two (n = 4), three (n = 2) or four (n = 1) additional family members presenting with hypodontia. Of the 77 oligodontia cases, two showed the same tooth agenesis pattern, while 75 patients showed unique tooth agenesis patterns. CONCLUSIONS: Despite familial aggregation and expected Mendelian segregation, the number of missing teeth in the familial hypo-/oligodontia phenotypes and the tooth agenesis patterns are highly variable between the affected family members. Therefore, we hypothesize that tooth agenesis is not (always) a simple monogenic condition, but additional genetic or environmental factors can modify the expression of the phenotype.

The influence of mixing methods and disinfectant on the physical properties of alginate impression materials.

The aims of this in vitro study were to quantify the effect of manual versus automatic mixing and of using a disinfectant on mechanical properties of three different alginate impression materials. Two of the three alginates tested were especially developed for orthodontic use: Orthotrace® and Orthofine® while the third was a conventional alginate CA37FS®. Alginates were mixed by hand or automatically using a Cavex alginate mixer II®. Mixing was performed at room temperature using tap water. The material was allowed to set in a water bath at 35°C (±1°C), simulating intra-oral setting conditions, and half of the samples were disinfected before testing. For each tested material, 10 standardized samples were used. The disinfectant used was the CavexImpreSafe® that has a bactericide, virucide, and fungicide function. The specimens were exposed for 3 minutes in a 3% solution and were then tested according to the ISO 1563: 1990 (E) standard specifications. Descriptive statistics and three-way analysis of variance were performed, and a 5% significance level was used for statistical analysis. Evaluation of tensile strength and elastic recovery of different alginate samples, hand versus automatical mixing or disinfected versus not disinfected, resulted in significant differences for all materials except for Orthofine®. Considering detail reproduction, all three alginates evaluated reproduced the 50-µm line successfully without interruption. The mixing method can significantly affect the elastic recovery and tensile strength of the alginates tested while the effect of using a disinfectant is less explicit.