A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement.

BACKGROUND: Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. METHODS: We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. RESULTS: We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. CONCLUSIONS: We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. TRIAL REGISTRATION NUMBERS: NCT01746121 and NCT02397824.

Social vulnerability in paediatric dentistry: an overview of ethical considerations of therapeutic patient education.

Dental caries is a multifactorial condition that remains a major public health issue in high income countries. The prevalence of dental caries in children has markedly declined in most countries over the past 30 years. However, the disease continues to affect a vulnerable population defined as a high-risk group. As many public health policies are inefficient in dealing with this underprivileged group, it is necessary to find other strategies to decrease the incidence and the burden of dental caries. Defining dental caries as a chronic disease enables us to develop the concept of 'therapeutic patient education.' It is meant to train patients to self-manage or adapt treatment to their particular chronic disease and to cope with new processes and skills. The purpose of this paper is to propose a new approach to dental caries, in particular to early childhood caries. That should decrease the gravity and prevalence of the disease in this specific population. As a result, this new approach could increase the quality of life of many children both in terms of function and aesthetics.

Emergence of permanent teeth: secular trends and variance in a modern sample.

The purpose of this study was to update the most commonly used tables of dental eruption (emergence), which are more than 50 years old and do not distinguish between ethnic and socio-economic groups. Clinical emergence data was collected for a modern sample of 574 French children and adolescents, aged 5.5 years to 15 years (294 girls and 280 boys). With respect to the present sample, the commonly used eruption tables of Hurme were accurate for most aspects of mandibular emergence, but were seriously flawed for the maxillary arch. Emergence of all permanent maxillary teeth varied by at least 3 months from Hurme's means; lateral incisors, canines, and second molars erupted earlier, but both premolars emerged later. Compared to similar French data collected in 1958, there appears to be a secular trend for later eruption of the maxillary premolars and earlier emergence of permanent second molars. These changes may reflect an evolutionary reduction in the size of the maxilla, a progressive decrease in genetic control of permanent canines, as well as first and second premolars, and/or progress in dental preventive measures to conserve primary molars. From a clinical perspective, appropriate dental emergence data are essential for effectively intercepting developmental malocclusions in children and adolescents.

[Planning dental care and orthodontic treatment for children afflicted with malignant hematological diseases]. / Planification des soins bucco-dentaires et des traitements ODF chez les enfants atteints d'une hémopathie maligne.

THE PROBLEM: In France, cancer affects 1 to 3% of all children and represents the second most frequent cause of mortality among children younger than fifteen. Malignant blood diseases are the most frequently occurring childhood cancers. Although their mortality rate has been tending to decrease, they often seem to develop after "opportunistic" latent infections persist, undetected, in un-eradicated sites that may be of dental origin. This infectious risk, frequently undiagnosed in hospitals, should be of concern to both general dentists and orthodontists. OBJECTIVES: General dentists and orthodontists each have specific roles to play in teaching children about oral health at an early age and in detecting and eradicating infection as well as in seeing at risk children in regular follow-up visits. DISCUSSION: Dentists should examine children on regularly scheduled preventive appointments and treat dental caries when they discover it. Orthodontists, who see the children they are treating on frequently scheduled appointments, should always be on the alert for incipient caries in their patients and be careful to make the appliances they wear as well fitting and non-irritating as possible to minimize the risk of inflammation and development of sore spots. Both dentists and orthodontists should teach their patients how to maintain healthy diets and good oral hygiene. They may be called upon to provide local relief for acute lesions that chemotherapy sometimes causes in the soft tissues of patients with hematological cancers and to modify irritating appliances.