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Add Angelman, Prader-Willi and Dup15q Syndromes to the Early Check Newborn Screening Panel

$154,082.25 2021

Add Angelman, Prader-Willi and Dup15q Syndromes to the Early Check Newborn Screening Panel

Anne Wheeler, PhD

Angelman syndrome (AS), Prader-Willi syndrome (PWS), and Dup15q syndrome are largely caused by aberrant inheritance of imprinting markers at the 15q11-13 locus resulting in disruption of gene regulation. The conditions have different etiologies but share diagnostic options and are targets for emerging therapeutics. The average age of diagnosis ranges from 6 months for infants with PWS to 3 years for children with Dup15q, and much later for cases with nondeletion subtypes of PWS or AS. Existing molecular methodologies can identify the majority of cases of all three conditions by interrogating DNA methylation patterns at the SNRPN/UBE3A locus. Newborn screening (NBS) provides the only population-based strategy to implement such testing broadly and identify infants who could benefit from early disease detection and treatment. However, a prospective population-based pilot study is needed to demonstrate feasibility of large-scale NBS and evaluate screening and follow-up protocols for public health implementation. Early Check, an ongoing voluntary NBS program in North Carolina, provides an opportunity to screen for a variety of rare disorders, provide short- and long-term follow-up services to identified infants, and generate data to inform public policy. This study focuses on the necessary preparatory steps that we are taking to add screening for PWS, AS and Dup15q to the Early Check Program to make prospective screening available to the parents of all ~120,000 newborns in the state.