De novo variants in the essential splicing factor gene SRSF3 cause variable developmental phenotypes.

De novo variants in SRSF3 are linked to variable developmental phenotypes, including developmental delay and intellectual disability, in nine affected individuals.

• Why it matters: Understanding how mutations in a key splicing factor contribute to developmental disorders can reveal mechanisms underlying phenotypic variability and inform diagnosis and potential interventions.
• What they did: The study identified nine individuals with de novo SRSF3 variants affecting conserved residues, and conducted molecular analyses including RT-PCR, RNA-seq, and functional studies in cell models to assess transcript stability, protein interactions, and nucleocytoplasmic shuttling.
• The result: Distinct functional defects in SRSF3 variants, such as reduced RNA binding, protein instability, and impaired nucleocytoplasmic shuttling, may explain the phenotypic variability observed in affected individuals.