Pathogenic Variants in RNU2-2, a Non-coding Spliceosomal RNA, Cause a Distinctive Developmental and Epileptic Encephalopathy

Abstract

RNU2-2 is a non-coding small nuclear RNA (snRNA) that forms part of the spliceosome. We identified recurrent pathogenic RNU2-2 variants in 4 of 672 (0.6%) patients with developmental and epileptic encephalopathies (DEEs) of unknown cause. An additional patient was subsequently included. Patients with RNU2-2 DEE had median seizure onset age of 24 months, focal and generalized seizures, status epilepticus (n = 5), severe to profound impairment, hyperventilation (n = 3), and obstructive sleep apnea (n = 3). Electroencephalography showed sleep-activated multifocal epileptiform discharges (n = 4) and hippocampal sclerosis on magnetic resonance imaging (n = 3). Pathogenic variants in RNU2-2 cause ..