Genome sequencing improves diagnostic yield for developmental and epileptic encephalopathies by identifying structural and non-coding variants missed by exome or gene panel testing.

medRxiv · Apr 28, 2026 · PreprintGenetic & Genomic Medicine

Systematic analysis of snRNA genes reveals frequent RNU2-2 variants in dominant and recessive developmental and epileptic encephalopathies

Elsa Leitão, Amandine Santini, Benjamin Cogné, Miriam Essid, Maria Athanasiadou, Christy W. LaFlamme, Pierre Marijon, Virginie Bernard, Kévin Jousselin, Nicolas Chatron, Giulia Barcia, Boris Keren, Cyril Mignot, Perrine Charles, Thomas Besnard, , Johanna Herwig

The paper identifies RNU2-2 variants as a frequent cause of neurodevelopmental disorders, both dominant and recessive, in a large cohort of individuals with rare disorders.

Nature Genetics · Mar 30, 2026Peer-reviewedGenetic & Genomic Medicine

Diagnostic Utility of Genome-wide DNA Methylation Analysis in Genetically Unsolved Developmental and Epileptic Encephalopathies and Refinement of a CHD2 Episignature

Christy W. LaFlamme, Cassandra Rastin, Soham Sengupta, Helen E. Pennington, Sophie J. Russ-Hall, Amy Schneider, Emily S. Bonkowski, Edith P. Almanza Fuerte, Talia J. Allan, Miranda Galey, Joy Goffena, Sophia B Gibson, Denis M. Nyaga, Nico Lieffering, Malavika Hebbar, , Heather C. Mefford

This study evaluates genome-wide DNA methylation analysis in genetically unsolved DEEs, identifying 10 causative or candidate genetic causes and refining a CHD2 episignature.

Nature Communications · Aug 6, 2024Peer-reviewedGenetic & Genomic Medicine