Three Genes Associated with Neurodevelopmental Disorders Identified in New Study

The Journal of Clinical Investigation (Li, D., et al.) 11.14.2023, published “Spliceosome malfunction causes neurodevelopmental disorders with overlapping features.” The article discusses neurodevelopmental disorders arise during childhood (NDDs), a diverse group including autism spectrum disorder and intellectual disability. Over 1,500 genes linked to these conditions have been identified , notably those regulating gene expression and chromatin structure. Despite progress in genetic diagnoses, understanding how these genes interact and cause neurodevelopmental impairments remains a challenge.

The focus shifts to alternative splicing—a crucial process in gene expression—where errors in this mechanism due to genetic mutations can significantly impact brain development and function.  This study explores the role of certain genes (U2AF2 and PRPF19) encoding spliceosomal subunits in neurodevelopmental disorders. Researchers discovered variants in these genes in individuals with NDDs, leading to shared neurological and developmental traits, including delays, intellectual disabilities, seizures, and distinct facial features. 

Genetic sequencing, protein analysis, and cell modeling were used to unravel the impact of these gene variants on neurodevelopment. The study identified potential downstream effects, linking these spliceosomal genes to the regulation of other genes involved in neural development.  Similar missense variants in the RBFOX1 gene in individuals with comparable neurodevelopmental features were found, further strengthening the association between these genes and NDDs.

The study provides insights into shared genetic mechanisms underlying NDDs, paving the way for potential therapeutic targets and better understanding these complex disorders.

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For more information:

Read the full article on the Journal of Clinical Investigation website here.

Read additional articles on autism and Lyme on LDA’s website here.