Rare-ID: The First Neonate Diagnostic Approach Using Genome Sequencing for Complex Pediatric Cases in a Greek Cohort

Newborn screening using biochemical tests is a widespread practice. However, the recent availability of genetic sequencing has enabled the rapid screening of many monogenic disorders. The purpose of our study was to assess the outcomes of whole exome sequencing (WES) and whole genome sequencing (WGS) as the primary newborn screening test. This cohort study enrolled 26 symptomatic neonates and infants exhibiting a spectrum of neurological symptoms and issues. Genome sequencing (GS) identified relevant diagnostic variants in 9 patients (point mutations, CNVs and one case of aneuploidy), suggesting that using GS as the primary newborn screening test in a general newborn population enhances traditional screening's detection capabilities. This evidence-based finding may support considering GS as a critical method for first-tier screening.