Systematic analysis of snRNA genes reveals frequent RNU2-2 variants in dominant and recessive developmental and epileptic encephalopathies - PubMed
7 hours ago
- #snRNA genes
- #epileptic encephalopathies
- #neurodevelopmental disorders
- Systematic analysis of 200 snRNA genes in a cohort of 34,329 individuals with rare disorders identifies RNU2-2 variants as a frequent cause of neurodevelopmental disorders (NDDs).
- RNU2-2 variants are found in 141 individuals, including 35 with dominant pathogenic variants and 91 affected members from 73 families with biallelic recessive variants, indicating recessive inheritance is at least twice as common as dominant.
- Both dominant and recessive RNU2-2 NDDs share overlapping clinical features, with epilepsy being a frequent manifestation, highlighting the gene's role in developmental and epileptic encephalopathies.
- Blood transcriptomics and DNA methylation analyses reveal variant-specific effects on splicing and episignatures, supporting a gradient-of-impact model that bridges dominant and recessive inheritance mechanisms.
- The study establishes RNU2-2 as a principal contributor to NDDs, with prevalence nearly as high as ReNU syndrome (caused by RNU4-2 variants), underscoring the significant role of noncoding RNA genes in genetic diseases.