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.journal articleresearch support, non-u.s. gov't2016 Feb2015 10 26importe

Buddies: A Structured Outdoor Play Curriculum in an Integrated Preschool

Play is the natural context in which children with neuroptypical development (NTD) hone their communication and social interaction skills. It is precisely these key developmental areas in which children with a diagnosis of Autism Spectrum Disorder (ASD) present with deficits (American Psychiatric Association, 2013). Early childhood education centers typically offer daily outdoor recess times in which children are given the opportunity to play outside (Georgia Department of Early Care and Learning, 2016). However, the curriculum during recess is often unstructured and adult staffing is reduced. (Kasari, Rotheram-Fuller, Locke, & Gulsrud, 2012). This lack of a structured activity time, which could otherwise be used for focused treatment, lends to children with ASD experiencing difficulties engaging in play, due to engagement in repetitive and compulsive behaviors, and impulsiveness that may be more motivating (Peeters 1997; Veale 1998). Unstructured periods of time during the school day are missed opportunities for needed social skills treatment for children with ASD. This study, conducted in an integrated preschool setting across four age groups, examines if a structured, cooperative outdoor play curriculum with a focus on natural modeling and imitation, increases the rate that children with ASD are in proximity to typically developing peers, increases the number of social bids from children with ASD to peers with NTD, and increases the number of social bids from children with NTD to peers with ASD, in both outdoor recess and indoor free-play sessions. This study is currently being conducted, however it is hypothesized that children, both with ASD and NTD, will increase these defined behaviors

Teaching and Learning within and across Cultures: Educator Requirements across the United States

The article addresses the treatment of multicultural education in U.S. teacher education programs, as of 2007. The authors believe there is a need for state-level requirements for meaningful multicultural education for preservice teachers, and they present their study describing the development and implementation of such a requirement in Georgia. Their study investigates three major themes in teacher education present in the U.S. as of 2004: separate certification for multicultural education, multicultural education embedded in bilingual education, and fully embedded cross-cultural education. They explain their survey of teacher education programs in Georgia, they describe the state reforms that resulted from their research, and they present their recommendations for future reform

Racial/Ethnic Disparities in the Identification of Children With Autism Spectrum Disorders

Objectives. We sought to examine racial and ethnic disparities in the recognition of autism spectrum disorders (ASDs)

SPARK: A US Cohort of 50,000 Families to Accelerate Autism Research

The Simons Foundation Autism Research Initiative (SFARI) has launched SPARKForAutism. org, a dynamic platform that is engaging thousands of individuals with autism spectrum disorder (ASD) and connecting them to researchers. By making all data accessible, SPARK seeks to increase our understanding of ASD and accelerate new supports and treatments for ASD