Novel Study Unveils Autism's Genetic Origins and Treatment Prospects

April 14, 2024

Autism spectrum disorder (ASD) encompasses a range of neurodevelopmental conditions characterized by repetitive behaviors and impaired social interaction. Genetic factors play a significant role in ASD development, with recent studies implicating genes involved in chromatin modification and gene transcription.

One such gene, KMT2C (lysine methyltransferase 2c), encoding a catalytic unit of the H3K4 (histone H3 lysine 4) methyltransferase complex, has emerged as a key player in ASD and related neurodevelopmental disorders. Haploinsufficiency of KMT2C, where one functional copy of the gene is lacking, has been identified as a risk factor for ASD. However, the precise molecular mechanisms underlying how loss-of-function mutations in KMT2C contribute to these conditions remain elusive.

To search for more knowledge in this matter, a collaborative team from Juntendo University, RIKEN, and the University of Tokyo conducted a groundbreaking study published in the journal Molecular Psychiatry on March 26, 2024. Led by Professor Tadafumi Kato from Juntendo University Graduate School of Medicine, the research team, including Dr. Takumi Nakamura and Dr. Atsushi Takata from the RIKEN Center for Brain Science, and Professor Takashi Tsuboi from The University of Tokyo's Graduate School of Arts and Sciences, aimed to unravel the molecular intricacies underlying KMT2C's role in ASD pathogenesis.

The team investigated KMT2C's role in ASD using genetically modified mice (Kmt2c+/fs) with a mutation mimicking KMT2C haploinsufficiency. Behavioral tests showed these mice had reduced social behavior, inflexibility, auditory sensitivity, and cognitive issues, mirroring ASD symptoms.