Non-random distribution of deleterious mutations in the DNA and protein-binding domains of IRF6 are associated with Van Der Woude syndrome

Background: The development of the face occurs during the early days of intrauterine life by the formation of facial processes from the first Pharyngeal arch. Derangement in these well-organized fusion events results in Orofacial clefts (OFC). Van der Woude syndrome (VWS) is one of the most common causes of syndromic cleft lip and/or palate accounting for 2% of all cases. Mutations in the IRF6 gene account for 70% of cases with the majority of these mutations located in the DNA-binding (exon 3, 4) or protein-binding domains (exon 7-9). The current study was designed to update the list of IRF6 variants reported for VWS by compiling all the published mutations from 2013 to date as well as including the previously unreported VWS cases from Africa and Puerto Rico.Methods: We used PubMed with the search terms; "Van der Woude syndrome," "Popliteal pterygium syndrome," "IRF6," and "Orofacial cleft" to identify eligible studies. We compiled the CADD score for all the mutations to determine the percentage of deleterious variants.Results: Twenty-one new mutations were identified from nine papers. The majority of these mutations were in exon 4. Mutations in exon 3 and 4 had CADD scores between 20 and 30 and mutations in exon 7-9 had CADD scores between 30 and 40. The presence of higher CADD scores in the protein-binding domain (exon 7-9) further confirms the crucial role played by this domain in the function of IRF6. In the new cases, we identified five IRF6 mutations, three novel missense mutations (p.Phe36Tyr, p.Lys109Thr, and p.Gln438Leu), and two previously reported nonsense mutations (p.Ser424*and p.Arg250*).Conclusion: Mutations in the protein and DNA-binding domains of IRF6 ranked among the top 0.1% and 1% most deleterious genetic mutations, respectively. Overall, these findings expand the range of VWS mutations and are important for diagnostic and counseling purposes.</p

Initiative en santé buccodentaire des enfants : le point de vue des intervenants quant à ses effets dans les communautés des Premières Nations

IntroductionDepuis 2004, l’équipe de l’Initiative en santé buccodentaire des enfants (ISBE) oeuvre dans de nombreuses communautés inuites et des Premières Nations du Canada à remédier aux disparités en matière de santé buccodentaire, en particulier en ce qui concerne la carie de la petite enfance. Alliant prévention et dentisterie peu invasive, l’approche communautaire de l’ISBE améliore la santé buccodentaire dans la petite enfance. Le programme a pour but de réduire le plus possible le fardeau de la maladie buccodentaire, en particulier d’éviter les opérations chirurgicales. Nous avons étudié les résultats du programme au sein des communautés des Premières Nations du Manitoba du point de vue du personnel de l’ISBE. MéthodologieDes thérapeutes dentaires et des aides dentaires oeuvrant dans des communautés des Premières Nations ont participé à trois groupes de discussion et à une entrevue semi-structurée approfondie. Les données rassemblées ont été analysées par thème. RésultatsDes thèmes convergents propres aux professionnels des soins dentaires sont ressortis des données obtenues auprès de 22 participants. Les participants ont indiqué que les thérapeutes dentaires et les aides dentaires offrent un accès à des soins buccodentaires de base dans les communautés : l’évaluation de la santé buccodentaire, le nettoyage des dents, l’application de vernis fluoré et la pose d’agents de scellement. Les participants étaient d’accord pour affirmer que l’éducation, l’information et des relations culturellement appropriées avec les parents sont cruciales pour la prestation d’un soutien continu et le renforcement des capacités au sein des programmes communautaires. Parmi les défis mentionnés, il y a le peu d’inscriptions au programme, les difficultés d’accès aux domiciles et d’obtention du consentement, le manque de ressources humaines et l’insuffisance des occasions d’apprentissage offertes aux aides dentaires. ConclusionDans l’ensemble, les participants ont indiqué que l’ISBE contribuait favorablement à la santé buccodentaire dans la petite enfance au sein des communautés des Premières Nations. Cependant, une offre accrue en matière de formation du personnel dentaire au sein des communautés, le fait que les membres des communautés soient au courant de l’existence du programme et la participation des parents en vue de processus de prestation et de consentement culturellement appropriés seraient essentiels à l’amélioration des résultats du programme

Children’s Oral Health Initiative: workers’ perspectives on its impact in First Nations communities

IntroductionSince 2004, the Children’s Oral Health Initiative (COHI) has been working in many First Nations and Inuit communities in Canada to address oral health disparities, specifically early childhood caries (ECC). The COHI community-based approach improves early childhood oral health (ECOH) by balancing prevention with minimally invasive dentistry. The goal is to reduce the burden of oral disease, mainly by minimizing the need for surgery. We investigated program success in First Nations communities in the province of Manitoba, from the perspective of COHI staff. MethodsFirst Nations community-based dental therapists and dental worker aides participated in three focus groups and an in-depth semistructured interview. The collected data were thematically analyzed. ResultsData from 22 participants yielded converging and practitioner-specific themes. Participants reported that dental therapists and dental worker aides provide access to basic oral care in their communities including oral health assessments, teeth cleaning, fluoride varnish applications and sealants. The participants agreed that education, information sharing and culturally appropriate parental engagement are crucial for continuous support and capacity building in the community programs. Low enrolment, difficulty accessing homes and getting consent, limited human resources as well as lack of educational opportunities for dental worker aides were identified challenges. ConclusionOverall, the participants reported that the COHI program positively contributes to ECOH in First Nations communities. However, increased community-based training for dental workers, community awareness about the program, and engagement of parents to facilitate culturally appropriate programming and consent processes are critical to improving program outcomes