Biallelic variants in RNU2-2 cause the most prevalent known recessive neurodevelopmental disorder - PubMed
7 hours ago
- #RNU2-2
- #neurodevelopmental disorder
- #genetics
- Biallelic variants in RNU2-2 are identified as the most prevalent known recessive neurodevelopmental disorder (NDD).
- Genetic association supports a recessive model with a log Bayes factor of 18.2, and 17 rare variants have high pathogenicity probability (>0.8), involving 18 probands and 5 affected siblings.
- Affected individuals exhibit intellectual disability, global developmental delay, and seizures.
- Recessive RNU2-2 syndrome accounts for ~10% of recessive NDD families diagnosable by sequencing, affecting ~60% as many families as dominant RNU4-2-related ReNU syndrome.
- Variants are predicted to destabilize U2-2 snRNA structures, and RNA sequencing shows >90% reduction in pathogenic U2-2 allele expression in biallelic cases, indicating a loss-of-expression mechanism.