Exploring the connection between RNA splicing and intellectual disability

Abstract

Intellectual disability (ID) is a broad diagnostic category that encompasses individuals with impaired cognitive ability. While these disorders have heterogeneous causes, recent developments in next-generation sequencing (NGS) are revealing the prevalence of genetic etiologies. In particular, germline mutations in genes that affect RNA splicing are increasingly common causes of ID disorders. Research to elucidate the functional relationship between splicing and neurodevelopment is critical since molecular therapeutics require a nuanced understanding of the pathological mechanism. In this review, we first summarize the trends that have led to the discovery of the RNA splicing–ID relationship, then discuss recent progress and future directions for research surrounding RNA splicing in neurodevelopment. Finally, we speak on how these results may serve as the foundation for burgeoning therapies.