Browsing by Author "McCormick, David"

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    Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections
    (Elsevier, 2024) Jeffries, Lauren; Mis, Emily K.; McWalter, Kirsty; Donkervoort, Sandra; Brodsky, Nina N.; Carpier, Jean-Marie; Ji, Weizhen; Ionita, Cristian; Roy, Bhaskar; Morrow, Jon S.; Darbinyan, Armine; Iyer, Krishna; Aul, Ritu B.; Banka, Siddharth; Chao, Katherine R.; Cobbold, Laura; Cohen, Stacey; Custodio, Helena M.; Drummond-Borg, Margaret; Elmslie, Frances; Finanger, Erika; Hainline, Bryan E.; Helbig, Ingo; Hewson, Stacy; Hu, Ying; Jackson, Adam; Josifova, Dragana; Konstantino, Monica; Leach, Meganne E.; Mak, Bryan; McCormick, David; McGee, Elisabeth; Nelson, Stanley; Nguyen, Joanne; Nugent, Kimberly; Ortega, Lucy; Goodkin, Howard P.; Roeder, Elizabeth; Roy, Sani; Sapp, Katie; Saade, Dimah; Sisodiya, Sanjay M.; Stals, Karen; Towner, Shelley; Wilson, William; Deciphering Developmental Disorders; Genomics England Research Consortium; Undiagnosed Disease Network; Khokha, Mustafa K.; Bönnemann, Carsten G.; Lucas, Carrie L.; Lakhani, Saquib A.; Medical and Molecular Genetics, School of Medicine
    Purpose: We sought to delineate a multisystem disorder caused by recessive cysteine-rich with epidermal growth factor-like domains 1 (CRELD1) gene variants. Methods: The impact of CRELD1 variants was characterized through an international collaboration utilizing next-generation DNA sequencing, gene knockdown, and protein overexpression in Xenopus tropicalis, and in vitro analysis of patient immune cells. Results: Biallelic variants in CRELD1 were found in 18 participants from 14 families. Affected individuals displayed an array of phenotypes involving developmental delay, early-onset epilepsy, and hypotonia, with about half demonstrating cardiac arrhythmias and some experiencing recurrent infections. Most harbored a frameshift in trans with a missense allele, with 1 recurrent variant, p.(Cys192Tyr), identified in 10 families. X tropicalis tadpoles with creld1 knockdown displayed developmental defects along with increased susceptibility to induced seizures compared with controls. Additionally, human CRELD1 harboring missense variants from affected individuals had reduced protein function, indicated by a diminished ability to induce craniofacial defects when overexpressed in X tropicalis. Finally, baseline analyses of peripheral blood mononuclear cells showed similar proportions of immune cell subtypes in patients compared with healthy donors. Conclusion: This patient cohort, combined with experimental data, provide evidence of a multisystem clinical syndrome mediated by recessive variants in CRELD1.
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    How Can Public Health Leaders Improve School Compliance with the Indiana Department of Health Mandatory Vaccine Requirements for School-Aged Populations?
    (2023) Carlson, Megan Marie; Stone, Cynthia; Silverman, Ross; McCormick, David
    Primary and Secondary Schools in the United States have consistently served as a safety net to prevent outbreaks of vaccine-preventable diseases, with state policy enactment requiring vaccines for school entry. While states have long implemented vaccination mandates for schools as a public health measure, the enforcement of those mandates by states and schools has been inconsistent. Over the past few years, there has been a significant decline in the vaccination rates among Indiana children, which was recently accelerated by the COVID-19 pandemic. Public health officials and legislatures continue to adopt policies and laws to combat growing vaccine noncompliance and non-medical exemption requests. However, an essential component of this process is being overlooked, the implications for schools, particularly for schools without a medical professional on staff. The purpose of this study is to gather qualitative insights from school personnel regarding perceptions, challenges, and barriers impacting the enforcement of state-mandated school entry vaccines. The overall aim of this study is to draw on the experiences of these key participants and ‘experts’ to inform public health interventions or policy changes that will support improved vaccination reporting and compliance among school systems. The Consolidated Framework for Implementation Research (CFIR) framework was used to examine the implementation of the school vaccine mandate by school personnel who played a role in the vaccine requirement process. Semi-structured interviews were conducted with a range of personnel (n=25) supporting medical, non-medical, and administrative roles within a public or charter school or district. Interview Guides for the semi-structured interviews were developed focusing on known current processes of school vaccine mandates applied to constructs within the Inner Setting domain. Responses were categorized into themes based on eleven constructs from the CFIR Inner Setting domain. Findings show school personnel experience a variety of conditions, challenges, and barriers impacting their abilities to comply with state vaccine requirements. Findings also yielded several considerations for facilitators to improve vaccination uptake. A plan for change to improve vaccination rates through a policy analysis and subsequent policy change is presented.