Researchers at Juntendo University in Tokyo, Japan, have made significant progress in understanding the genetic basis of autism spectrum disorder (ASD). Their study on mice with a frameshift mutation in the KMT2C gene revealed behavioral and cognitive impairments similar to symptoms seen in individuals with ASD.
The researchers found that the mutation in the KMT2C gene, leading to haploinsufficiency, resulted in increased expression of genes associated with ASD risk. This unexpected discovery suggests indirect effects on gene expression due to KMT2C haploinsufficiency. Interestingly, treatment with the drug vafidemstat showed promise in correcting these abnormalities, offering a potential therapeutic avenue for ASD and related conditions.
ASD encompasses a range of neurodevelopmental conditions characterized by repetitive behavior and difficulties with social interactions. Genetic factors have been identified as playing a role in the development of ASD, with genes involved in chromatin modification and gene transcription implicated in the disorder’s pathogenesis.
Among these genes, KMT2C has been linked to the development of autism and other neurodevelopmental disorders. Studies have shown that haploinsufficiency of KMT2C is a risk factor for ASD, but the molecular mechanisms underlying this relationship have remained unclear.
To bridge this gap in knowledge, the research team from Juntendo University, RIKEN, and the University of Tokyo conducted a landmark study published in the journal Molecular Psychiatry. Lead by Professor Tadafumi Kato, the team investigated how KMT2C haploinsufficiency contributes to ASD by studying genetically engineered mice with a frameshift mutation in the gene.
Behavioral analyses of the mutant mice revealed lower levels of social interaction, inflexibility, auditory hypersensitivity, and cognitive impairments – all characteristic of ASD. Transcriptomic and epigenetic profiling further unveiled that genes associated with increased ASD risk showed elevated expression in the mutant mice.
The researchers’ findings challenged existing beliefs about the potential for treating ASD and demonstrated the effectiveness of vafidemstat in improving ASD-like behaviors in the mutant mice. This breakthrough paves the way for future research to explore pharmacological treatments for ASD and related disorders, offering hope for individuals affected by these conditions.
In conclusion, the study sheds new light on the genetic underpinnings of ASD and highlights the potential for targeted interventions to address the core symptoms of the disorder. The researchers’ findings provide a foundation for further investigations into novel therapeutic approaches that could benefit individuals with ASD and other neurodevelopmental disorders.