From the Research
Mutations in the RBFOX gene can lead to neurodevelopmental disorders, including autism spectrum disorders, epilepsy, and intellectual disability, by disrupting normal brain development and function, particularly affecting synaptic function and neuronal communication. The RBFOX family of RNA-binding proteins (RBFOX1, RBFOX2, and RBFOX3) play a crucial role in regulating alternative splicing of neuronal genes, and their malfunction due to mutations can result in aberrant splicing outcomes 1.
Effects of RBFOX Mutations
- Disrupt normal brain development and function
- Cause neurodevelopmental disorders, such as autism spectrum disorders, epilepsy, and intellectual disability
- Affect synaptic function and neuronal communication
- Result in aberrant splicing outcomes, leading to changes in protein variants produced from certain genes
Current Treatment and Research
- Currently, there are no specific medications targeting RBFOX mutations directly
- Treatment focuses on managing symptoms through standard approaches for the resulting conditions, such as antiepileptic drugs for seizures or behavioral therapies for autism symptoms
- Genetic testing can identify these mutations, which may help guide family planning decisions and connect patients with appropriate clinical trials
- Research into RBFOX mutations is ongoing, with potential future therapies possibly including RNA-targeted approaches or gene therapy, though these remain experimental 2, 3
Recent Findings
- A recent study found that MeCP2, a key subunit of a higher-order multiunit protein complex, interacts with Rbfox proteins to regulate alternative splicing of critical genes, and defective MeCP2 in Rett syndrome mouse models disrupts this complex, leading to aberrant splicing outcomes 1
- Another study discovered that the CELF and RBFOX families of splicing factors have an ancient antagonism that tunes mRNA splicing outcomes, and this antagonism is conserved throughout evolution 4