Utility of Whole Genome Sequencing to Detect RNU4-2 Variants Associated with ReNU syndrome

BACKGROUND

• ReNU syndrome (RENU) is a neurodevelopmental disorder first described in 2024 characterized by global developmental delay, intellectual disability, seizures, brain anomalies, hypotonia, and other symptoms.
• RENU is estimated to account for 0.4% of all neurodevelopmental disorders and arises from variants in RNU4-2. Most RENU diagnoses have a common de novo n.64_65insT variant.
• RNU4-2 encodes spliceosome ribonucleoprotein U4 which is important for brain development.
• We present our clinical laboratory’s experience identifying a pathogenic RNU4-2 variant in a pediatric patient by whole genome sequencing (WGS).