Uncovering Phenotypic Expansion in AXIN2-Related Disorders through Precision Animal Modeling.

Heterozygous pathogenic variants in are associated with oligodontia-colorectal cancer syndrome (ODCRCS), a disorder characterized by oligodontia, colorectal cancer, and in some cases, sparse hair and eyebrows. We have identified four individuals with one of two , heterozygous variants (NM_004655.4:c.

Disparities in Telehealth Uptake for Developmental-Behavioral Pediatric Assessments by Preferred Family Language: A Developmental Behavioral Pediatrics Research Network Study.

Objective: Owing to the coronavirus disease 2019 (COVID-19) pandemic, many developmental-behavioral pediatric (DBP) practices adopted telehealth for care delivery. However, telehealth access and use for families with a preferred language other than English (PLOE) is an equity concern. Therefore, our study objective is to compare rates of telehealth utilization and visit completion by preferred family language among patients seen for DBP assessments during the COVID-19 pandemic.

Complex Autism Spectrum Disorder: Structural Determinants of Health and Their Impact on the Diagnosis.

Emmanuel is a 6.5-year-old boy who was referred to your evaluation clinic for concerns about his social skills and communication. He arrived in the United States (US) 1 year ago after an immigration trajectory that began in Haiti when he was aged 3 years; passed through Mexico, where the family was in various shelters for over a year; and concluded 2 years later, with the family eventually settling in an urban center in the northeastern United States.

Provider and Caregiver Perspectives on Telehealth Assessments for Autism Spectrum Disorder in Young Children: A Multimethod DBPNet Study Exploring Equity.

Background: Telehealth uptake increased dramatically during the COVID-19 pandemic, including for autism spectrum disorder (ASD) assessment by developmental-behavioral pediatric (DBP) clinicians. However, little is known about the acceptability of telehealth or its impact on equity in DBP care.

Objective: Engage providers and caregivers to glean their perspectives on the use of telehealth for ASD assessment in young children, exploring acceptability, benefits, concerns, and its potential role in ameliorating or exacerbating disparities in access to and quality of DBP care.

Developmentally-Trained Primary Care Clinicians: A Pipeline to Improved Access?

Objective: The purpose of this study is to decrease wait time and improve access to developmental-behavioral pediatric (DBP) evaluation in children 4 years of age and younger as part of a quality improvement (QI) initiative in an urban safety-net hospital.

Methods: A primary care pediatrician received DBP minifellowship training 6 hours per week for 1 year to become a developmentally-trained primary care clinician (DT-PCC). DT-PCCs then conducted developmental evaluations that consisted of using a Childhood Autism Rating Scale and Brief Observation of Symptoms of Autism to evaluate children 4 years and younger referred within the practice.

Access to Care After Autism Diagnosis During the COVID-19 Pandemic: A Quality Improvement Project.

Objective: The aim of this study was to identify barriers and improve access to services for children diagnosed with autism spectrum disorder (ASD) during the COVID-19 pandemic.

Methods: Sixty-two patients diagnosed with ASD between March 23 and June 30, 2020, at a large urban safety net hospital were identified by chart review. Patients were called from January to March 2021 and queried regarding access to services.

Three-dimensional microCT imaging of mouse heart development from early post-implantation to late fetal stages.

Comprehensive detailed characterization of new mouse models can be challenging due to the individual focus involved in developing these models. Often models are engineered to test a specific hypothesis in a limited number of tissues, stages, and/or other contexts. Whether or not the model produces the desired phenotypes, phenotyping beyond the desired context can be extremely work intensive and these studies are often not undertaken.

Raising the Question: Medication Mix-Up or Diversion.

Max is an 8-year-old boy with autism spectrum disorder and long-standing challenges with sleep maintenance, the latter of which persist despite behavioral intervention and environmental modification. When Max wakes in the early morning hours, he tends to wander the house, which causes his mother to be awake to monitor his safety. Given the impact of Max's fragmented sleep on his functioning and that of his family, you begin a trial of gabapentin liquid to promote sleep maintenance.

Pilot Survey: Police Understanding of Autism Spectrum Disorder.

This piliot study assessed the experiences of police officers related to persons with Autism Spectrum Disorder (ASD) via a survey assessing prior experience, comfort, knowledge, and ability to identify autistic persons. Fifty-one officers completed the survey: 52.9% reported previous ASD training, 34.

Development of a Training Curriculum for Hospital Security About Autism Spectrum Disorder.

Objective: To evaluate whether a newly developed autism spectrum disorder (ASD)-training curriculum for hospital security officers improves comfort, knowledge, and practice.

Methods: Participants were security officers. The ASD-training curriculum was a 45-minute interactive session, adapted from trainings developed for other types of hospital providers.

A global Slc7a7 knockout mouse model demonstrates characteristic phenotypes of human lysinuric protein intolerance.

Lysinuric protein intolerance (LPI) is an inborn error of cationic amino acid (arginine, lysine, ornithine) transport caused by biallelic pathogenic variants in SLC7A7, which encodes the light subunit of the y+LAT1 transporter. Treatments for the complications of LPI, including growth failure, renal disease, pulmonary alveolar proteinosis, autoimmune disorders and osteoporosis, are limited. Given the early lethality of the only published global Slc7a7 knockout mouse model, a viable animal model to investigate global SLC7A7 deficiency is needed.

Human and mouse essentiality screens as a resource for disease gene discovery.

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties.

Collaborating with Families and Law Enforcement Agencies to Improve Outcomes for Individuals with Autism Spectrum Disorder.

Increased visibility of adverse encounters between individuals with autism spectrum disorder (ASD) and law enforcement (LE) has stimulated a dialog among providers. There are a variety of contributing factors to the increase, including the recognized lack of training of LE professionals on the needs of individuals with ASD and the paucity of awareness of resources by the families of these individuals. The aim of this article is to provide insight into developmental-behavioral pediatric professionals, to enhance safety and reduce adverse outcomes for individuals with ASD in schools and the community.

High Resolution Imaging of Mouse Embryos and Neonates with X-Ray Micro-Computed Tomography.

Iodine-contrast micro-computed tomography (microCT) 3D imaging provides a non-destructive and high-throughput platform for studying mouse embryo and neonate development. Here we provide protocols on preparing mouse embryos and neonates between embryonic day 8.5 (E8.

Bi-allelic Variants in TONSL Cause SPONASTRIME Dysplasia and a Spectrum of Skeletal Dysplasia Phenotypes.

SPONASTRIME dysplasia is an autosomal-recessive spondyloepimetaphyseal dysplasia characterized by spine (spondylar) abnormalities, midface hypoplasia with a depressed nasal bridge, metaphyseal striations, and disproportionate short stature. Scoliosis, coxa vara, childhood cataracts, short dental roots, and hypogammaglobulinemia have also been reported in this disorder. Although an autosomal-recessive inheritance pattern has been hypothesized, pathogenic variants in a specific gene have not been discovered in individuals with SPONASTRIME dysplasia.

Live imaging of developing mouse retinal slices.

Background: Ex vivo, whole-mount explant culture of the rodent retina has proved to be a valuable approach for studying retinal development. In a limited number of recent studies, this method has been coupled to live fluorescent microscopy with the goal of directly observing dynamic cellular events. However, retinal tissue thickness imposes significant technical limitations.

Genome engineering: Drosophila melanogaster and beyond.

A central challenge in investigating biological phenomena is the development of techniques to modify genomic DNA with nucleotide precision that can be transmitted through the germ line. Recent years have brought a boon in these technologies, now collectively known as genome engineering. Defined genomic manipulations at the nucleotide level enable a variety of reverse engineering paradigms, providing new opportunities to interrogate diverse biological functions.

A piggyBac-based reporter system for scalable in vitro and in vivo analysis of 3' untranslated region-mediated gene regulation.

Regulation of messenger ribonucleic acid (mRNA) subcellular localization, stability and translation is a central aspect of gene expression. Much of this control is mediated via recognition of mRNA 3' untranslated regions (UTRs) by microRNAs (miRNAs) and RNA-binding proteins. The gold standard approach to assess the regulation imparted by a transcript's 3' UTR is to fuse the UTR to a reporter coding sequence and assess the relative expression of this reporter as compared to a control.

Ligand-independent activation of the Hedgehog pathway displays non-cell autonomous proliferation during eye development in Drosophila.

Deregulation of the Hedgehog (Hh) signaling pathway is associated with the development of human cancer including medullobastoma and basal cell carcinoma. Loss of Patched or activation of Smoothened in mouse models increases the occurrence of tumors. Likewise, in a Drosophila eye model, deregulated Hedgehog signaling causes overgrowth of eye and head tissues.

Second chromosome genes required for heart development in Drosophila melanogaster.

Heart development is an evolutionarily conserved process. The cardiac organ of Drosophila melanogaster is the dorsal vessel, a linear contractile tissue with cellular and morphogenetic similarities to the primitive heart tube formed at an early stage of vertebrate heart formation. Abundant evidence shows comparable intercellular signaling pathways and transcription factor networks are utilized in Drosophila and vertebrates, to specify cardiac progenitor cells and instruct their differentiation and function in forming the mature heart.

folded gastrulation, cell shape change and the control of myosin localization.

The global cell movements that shape an embryo are driven by intricate changes to the cytoarchitecture of individual cells. In a developing embryo, these changes are controlled by patterning genes that confer cell identity. However, little is known about how patterning genes influence cytoarchitecture to drive changes in cell shape.