Greene et al., 2025 reported a total of 25 cases with recurrent de novo single-nucleotide mutations at nucleotide positions 4 and 35 of RNU2-2 presenting with a neurodevelopmental syndrome characterized by developmental delay, intellectual disability, autistic behavior, microcephaly, hypotonia, hyperventilation, dysmorphic features, and a severe and complex seizure phenotype. Analysis of R-loop forming regions in ribozyme, snoRNA, and snRNA genes, specifically in rare disease cohorts, in Jackson et al., 2025 identified a total of 27 individuals from the 100,000 Genomes Project, the Genomics England, National Genomics Research Library database, the Solve-RD resource, the Centre for Population Genetics in Australia database, and the South Korean Undiagnosed Diseases database with rare RNU2-2 variants within a region from 1 to 60 bp constrained for variants in gnomAD v4. Detailed clinical information was available for 7 of these individuals, who presented with a neurodevelopmental disorder characterized by developmental delay and/or intellectual disability (7/7 individuals), epilepsy/seizures (5/7), and autism spectrum disorder (3/7), in addition to other non-neurological phenotypes.
Molecular Function
Small nuclear RNAs (snRNAs), such as U2 snRNA, are components of the spliceosome complex, directing accurate removal of intronic sequences from pre-mRNAs. The human genome contains 2 functional U2 snRNA genes,RNU2-1 andRNU2-2.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Mutations in the small nuclear RNA gene RNU2-2 cause a severe neurodevelopmental disorder with prominent epilepsy
