Summary:- at Children’s Hospital of Philadelphia (CHOP) have made a significant breakthrough in understanding neurodevelopmental disorders (NDDs) by identifying three novel genes that contribute to these conditions. This discovery has the potential to pave the way for new diagnostic tools and therapeutic interventions.
NDDs are a group of disorders that affect brain development and can cause a wide range of challenges, including intellectual disability, autism, and epilepsy. Despite significant advances in research, the underlying causes of many NDDs remain unknown.
The CHOP study, published in the Journal of Clinical Investigation, used a combination of genomic sequencing, phenotyping, and modeling in fly and stem cells to investigate the genetic architecture of NDDs. The researchers identified three genes – U2AF2, PRPF19, and RBFOX1 – that, when mutated, can lead to NDDs.
Mutations in these genes were found to disrupt the function of the spliceosome, a protein complex responsible for removing introns (non-coding segments of DNA) from pre-mRNA, the precursor to messenger RNA (mRNA). mRNA carries the genetic information from DNA to ribosomes, where it is used to synthesize proteins. Disruption of splicing can lead to the production of abnormal proteins, which can have a detrimental impact on brain development and function.
The researchers further investigated the effects of these gene mutations in human stem cell and fly models. They found that mutations in U2AF2 and PRPF19 impaired neuritogenesis, the process by which neurons form protrusions called neurites, which are essential for communication between neurons. Additionally, mutations in U2AF2 and PRPF19 led to social deficits in fly models.
The study also identified RBFOX1 as a splicing factor that interacts with U2AF2 and PRPF19. Mutations in RBFOX1 were found to disrupt splicing and impair neuron function.
These findings provide new insights into the genetic mechanisms underlying NDDs and have the potential to lead to the development of targeted therapies. By understanding how these genes contribute to NDDs, researchers may be able to develop drugs that can correct splicing defects and improve brain function in individuals with these disorders.
The study also highlights the importance of international collaboration in NDD research. The CHOP study involved researchers from around the world, and their combined expertise was essential for making this significant breakthrough.
Ref:- NeuroscienceNews.com