Spliceosome defects and neurodevelopmental disorders

The spliceosome is the core molecular machinery for RNA splicing, and its dysfunction can disrupt gene expression programs during neurodevelopment. With the widespread application of whole-genome sequencing, transcriptome sequencing, and long-read sequencing, the spectrum of spliceosome-related neurodevelopmental disorders has been continuously expanding. This review summarizes the genetic features, clinical phenotypes, and molecular mechanisms of pathogenic variants at three levels of the spliceosome: small nuclear RNAs, small nuclear ribonucleoproteins, and spliceosome assembly/regulatory factors. It further discusses tissue selectivity and phenotypic heterogeneity of spliceosome-related disorders, and highlights emerging research strategies and advances in RNA-targeted therapies, with the aim of informing mechanistic exploration and clinical research.