Saturation genome editing of <i>RNU4-2</i> reveals distinct dominant and recessive neurodevelopmental disorders.

ABSTRACT: Recently, de novo variants in an 18 nucleotide region in the centre of RNU4-2 were shown to cause ReNU syndrome, a syndromic neurodevelopmental disorder (NDD) that is predicted to affect tens of thousands of individuals worldwide^1,2. RNU4-2 is a non-protein-coding gene that is transcribed into the U4 small nuclear RNA (snRNA) component of the major spliceosome³. ReNU syndrome variants disrupt spliceosome function and alter 5' splice site selection^1,4. Here, we performed saturation genome editing (SGE) of RNU4-2 to identify the functional and clinical impact of variants across the entire gene. The resulting SGE function scores, derived from variants' effects on cell fitness, discriminate ReNU syndrome variants from those observed

SUBMITTER: De Jonghe J 

PROVIDER: S-EPMC12036422 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature